Molecular Analysis of SALL1 Mutations in Townes-Brocks Syndrome
Open accessAbstract
Townes-Brocks syndrome (TBS) is an autosomal dominantly inherited malformation syndrome characterized by anal, renal, limb, and ear anomalies. Recently, we showed that mutations in the putative zinc finger transcription factor gene SALL1 cause TBS. To determine the spectrum of SALL1 mutations and to investigate the genotype-phenotype correlations in TBS, we examined 23 additional families with TBS or similar phenotypes for SALL1 mutations. In 9 of these families mutations were identified. None of the mutations has previously been described. Two of these mutations are nonsense mutations, one of which occurred in three unrelated families. Five of the mutations are short deletions. All of the mutations are located 5' of the first double zinc finger (DZF) encoding region and are therefore predicted to result in putative prematurely terminated proteins lacking all DZF domains. This suggests that only SALL1 mutations that remove the DZF domains result in TBS. We also present evidence that in rare cases SALL1 mutations can lead to phenotypes similar to Goldenhar syndrome. However, phenotypic differences in TBS do not seem to depend on the site of mutation.
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TBS is caused by heterozygous mutation of SALL1 creating frameshifts and loss of functional domains.
“TBS is caused by heterozygous mutation of SALL1 creating frameshifts and loss of functional domains and leading to a symptomatic triad of anal, thumb and ear malformations”
From Tetramerisation governs SALL transcription factor function in development and disease (2025) · cites this paper as [28]
The Frameshift Mutations section reports heterozygous SALL1 deletions that cause frameshifts, and the Summary predicts that the identified mutations produce proteins lacking double zinc-finger domains. But the Summary also reports nonsense mutations, which are not frameshifts; loss of the domains is predicted rather than demonstrated. (LLM, conf=0.88)
Experimental — accuracy not yet measuredPhenotypic data is only available for two TBS cases with mutations before or within the QID: one patient with the central symptomatic triad of TBS (313del) and the other (420del) only presenting milder symptoms including dysplastic ears, misplaced finger-like thumbs and reduced kidney clearance.
“phenotypic data is only available for two of these cases, one patient with the central symptomatic triad of TBS (313del 47 ) and the other (420del 28 ) only presenting milder symptoms including dysplastic ears, misplaced finger-like thumbs and reduced kidney clearance.”
From Tetramerisation governs SALL transcription factor function in development and disease (2025) · cites this paper as [28]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredMutations in SALL1 cause Townes-Brocks syndrome.
“TBS is caused by heterozygous mutation of SALL1 creating frameshifts and loss of functional domains and leading to a symptomatic triad of anal, thumb and ear malformations”
From Tetramerisation governs SALL transcription factor function in development and disease (2025) · cites this paper as [28]
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Cites
Hereditary syndrome of imperforate anus with hand, foot, and ear anomalies
Townes, P. L., & Brocks, E. R. (1972) · The Journal of Pediatrics · doi:10.1016/s0022-3476(72)80302-0 · Cited by 174 · cited 2× · see citing works
“described by Townes and Brocks (1972) as an association of imperforate anus, supernumerary thumbs, mal-”
BackgroundKohlhase, J., Schuh, R., Dowe, G., Kühnlein, R. P., Jäckle, H., Schroeder, B., Schulz-Schaeffer, W., Kretzschmar, H. A., Köhler, A., Müller, U., et al. (1996) · Genomics · doi:10.1006/geno.1996.0631 · Cited by 145 · cited 1× · see citing works
“The SALL1 protein, however, contains four putative DNA binding domains (Kohlhase et al. 1996), and it remains to be shown which and how many of these are essential for gene function.”
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Research works printed but not linked: 1
- Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
Cited by
Sorted by citations
Okihiro syndrome is caused by SALL4 mutations
Kohlhase, J. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.23.2979 · Cited by 320 · see citing works
“stenosis, deafness and external ear anomalies (20).”
Self-citationTasse, C., Bohringer, S., Fischer, S., Lüdecke, H., Albrecht, B., Horn, D., Janecke, A., Kling, R., König, R., Lorenz, B., et al. (2005) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2005.04.015 · Cited by 220 · see citing works
Self-citationPaternal contribution to the risk for pre-eclampsia: Table 1
Zusterzeel, P. L. M., Morsche, R. T., Raijmakers, M. T. M., Roes, E. M., Peters, W. H. M., & Steegers, E. A. P. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.1.44 · Cited by 44 · see citing works
Investigation of meiotic rearrangements in DGS/VCFS patients with a microdeletion 22q11.2
Meiser, B., Butow, P., Barratt, A., Suthers, G., Smith, M., Colley, A., Thompson, E. M., & Tucker, K. L. (2000) · Journal of Medical Genetics · doi:10.1136/jmg.37.6.452 · Cited by 144
Variants of STAT6 (signal transducer and activator of transcription 6) in atopic asthma
GAO, P.-S., MAO, X.-Q., ROBERTS, M. H., ARINOBU, Y., AKAIWA, M., ENOMOTO, T., DAKE, Y., KAWAI, M., SASAKI, S., HAMASAKI, N., et al. (2000) · Journal of Medical Genetics · doi:10.1136/jmg.37.5.380a · Cited by 74 · see citing works
Lauberth, S. M., & Rauchman, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m513461200 · Cited by 140 · see citing works
Regulation and function of Spalt proteins during animal development
de Celis, J. F., & Barrio, R. (2009) · The International Journal of Developmental Biology · doi:10.1387/ijdb.072408jd · Cited by 137 · see citing works
Kiefer, S. M. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg233 · Cited by 124 · see citing works
“SALL1 mutations have been reported to have kidney defects, most commonly renal hypoplasia with or without cysts ( 9 ).”
BackgroundInfluentialSelf-citationKohlhase, J., Chitayat, D. A., Kotzot, D., Ceylaner, S., Froster, U. G., Fuchs, S., Montgomery, T., & Rösler, B. (2005) · Human Mutation · doi:10.1002/humu.20215 · Cited by 116 · see citing works
Self-citationSALL3, a new member of the human spalt-like gene family, maps to 18q23.
Kohlhase, J., Hausmann, S., Stojmenovic, G., Dixkens, C., Bink, K., Schulz-Schaeffer, W., Altmann, M., & Engel, W. (1999) · Genomics · doi:10.1006/geno.1999.6005 · Cited by 97 · see citing works
Self-citationEarly steps of paired fin development in zebrafish compared with tetrapod limb development
Mercader, N. (2007) · Development Growth & Differentiation · doi:10.1111/j.1440-169x.2007.00942.x · Cited by 92 · see citing works
“Mutations affecting Sall1 also lead to limb malformations in humans, known as Townes-Brocks syndrome (Kohlhase et al. 1998; Kohlhase et al. 1999).”
BackgroundCan hair be used to screen for breast cancer?
Kilinç, M., Ninis, V., Tolun, A., Estivill, X., Casals, T., Savov, A., Dağlı, E., Karakoc, F., Demirkol, M., Hüner, G., et al. (2000) · Journal of Medical Genetics · doi:10.1136/jmg.37.4.297 · Cited by 89
“mutations identified to date in TBS patients are located 5′ of the first double zinc finger encoding region.”
Aldudo, J., Bullido, M. J., & Valdivieso, F. (1999) · Human Mutation · doi:10.1002/(sici)1098-1004(199911)14:5 · Cited by 27 · see citing works
Kohlhase, J., Heinrich, M., Liebers, M., Fröhlich Archangelo, L., Reardon, W., & Kispert, A. (2002) · Cytogenetic and Genome Research · doi:10.1159/000071048 · Cited by 82 · see citing works
Self-citationMurine Sall1 represses transcription by recruiting a histone deacetylase complex
Kiefer, S. M., McDill, B. W., Yang, J., & Rauchman, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200052200 · Cited by 79 · see citing works
Tao, L., Boyd, M., Gonye, G., Malone, B., & Schwaber, J. F. (2000) · Human Mutation · doi:10.1002/1098-1004(200012)16:6
Self-citationBotzenhart, E., Green, A., Ilyina, H., König, R., Lowry, R. B., Lo, I. F. M., Shohat, M., Burke, L., McGaughran, J., Chafai, R., et al. (2005) · Human Mutation · doi:10.1002/humu.9362 · Cited by 72 · see citing works
“A chorioretinal coloboma has also been published in a single case to our knowledge, as well as Duane anomaly (Kohlhase et al., 1999; Rossmiller and Pasic, 1994).”
BackgroundMethodInfluentialSelf-citationsall4acts downstream oftbx5and is required for pectoral fin outgrowth
Harvey, S. A., & Logan, M. P. O. (2006) · Development · doi:10.1242/dev.02259 · Cited by 67 · see citing works
“The limb defects of individuals with TBS include preaxial polydactyly and triphalangeal thumb in the forelimbs, and syndactyly and club foot in the hindlimbs (Kohlhase et al., 1999).”
BackgroundEmbryonic expression of the murine homologue of SALL1, the gene mutated in Townes--Brocks syndrome.
Buck, A., Kispert, A., & Kohlhase, J. (2001) · Mechanisms of Development · doi:10.1016/s0925-4773(01)00364-1 · Cited by 65 · see citing works
Self-citationBotzenhart, E., Bartalini, G., Blair, E. M., Brady, A. F., Elmslie, F., Chong, K. L., Christy, K., Torres‐Martinez, W., Danesino, C., Deardorff, M. A., et al. (2007) · Human Mutation · doi:10.1002/humu.9476 · Cited by 57 · see citing works
“In a previous study (Kohlhase et al., 1999), it was suggested that most mutations occur in a “hot spot region” 5' to the coding region for the most aminoterminal double zinc finger domain.”
BackgroundMethodInfluentialSelf-citationGenetics of Hirschsprung disease and anorectal malformations
Mundt, E., & Bates, M. D. (2010) · Seminars in Pediatric Surgery · doi:10.1053/j.sempedsurg.2009.11.015 · Cited by 62 · see citing works
csal1 is controlled by a combination of FGF and Wnt signals in developing limb buds.
Farrell, E. R., & Münsterberg, A. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9852 · Cited by 57 · see citing works
Transcriptional Activation of the SALL1 by the Human SIX1 Homeodomain during Kidney Development*
Chai, L., Yang, J.-C., Di, C., Cui, W., Kawakami, K., Lai, R., & Ma, Y.-P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600180200 · Cited by 53
Ng, R., Matsumaru, D., Ho, A.-H., Garcia-Barcelo, M., Yuan, Z.-W., Smith, D., Kodjabachian, L., Tam, P., Yamada, G., & Lui, V. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.20 · Cited by 49
Holt-Oram syndrome: clinical and molecular description of 78 patients with TBX5 variants
Vanlerberghe, C., Jourdain, A., Ghoumid, J., Frénois, F., Mezel, A., Vaksmann, G., Lenne, B., Delobel, B., Porchet, N., Cormier‐Daire, V., et al. (2018) · European Journal of Human Genetics · doi:10.1038/s41431-018-0303-3 · Cited by 63 · see citing works
Borozdin, W., Steinmann, K., Albrecht, B., Bottani, A., Devriendt, K., Leipoldt, M., & Kohlhase, J. (2006) · Human Mutation · doi:10.1002/humu.9396 · Cited by 48 · see citing works
“Inclusion criteria for deletion analysis were (1) presence of at least one typical clinical major criterion for Townes-Brocks syndrome (Kohlhase et al., 1999c), (2) no other evident clinical diagnosis, and (3) previously negative SALL1 mutation analysis by direct sequencing (Kohlhase et al., 1999c).”
BackgroundInfluentialSelf-citationHox5 interacts with Plzf to restrict Shh expression in the developing forelimb
Xu, B., Hrycaj, S., McIntyre, D. C., Baker, N. C., Takeuchi, J., Jeannotte, L., Gaber, Z. B., Novitch, B. G., & Wellik, D. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315075110 · Cited by 54 · see citing works
“Forelimb defects similar to those seen in Hox5 mutants have been identified in patients with HOS caused by Tbx5 mutations (32–36), and Hox genes have been reported to be capable of driving Tbx5 expression (46), OS caused by Sall4 mutations (29, 30), Townes– Brocks syndrome caused by Sall1mutations (31, 47) and Saethre…”
BackgroundMutation of SALL2 causes recessive ocular coloboma in humans and mice
Kelberman, D., Islam, L., Lakowski, J., Bacchelli, C., Chanudet, E., Lescai, F., Patel, A., Stupka, E., Buck, A., Wolf, S., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt643 · Cited by 46 · see citing works
“Functional redundancy between Sall factors is likely to compensate for the heterozygous loss of Sall2 in the eye (33,34,50), particularly Sall1 which is expressed in the developing eye and can be associated with retinochoroidal coloboma in some cases of Townes-Brocks syndrome (48,51).”
BackgroundSelf-citationDisruption of teashirt zinc finger homeobox 1 is associated with congenital aural atresia in humans.
Feenstra, I., Vissers, L., Pennings, R., Nillessen, W., Pfundt, R., Kunst, H., Admiraal, R., Veltman, J., van Ravenswaaij-Arts, C. V., Brunner, H., et al. (2011) · American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.008 · Cited by 46 · see citing works
Drosophila spalt/spalt-related mutants exhibit Townes-Brocks' syndrome phenotypes
Dong, S. P. D., Todi, S. V., Eberl, D., & Boekhoff-Falk, G. (2003) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1836391100 · Cited by 46 · see citing works
Harrison, S. J., Nishinakamura, R., Jones, K. R., & Monaghan, A. P. (2011) · Disease Models & Mechanisms · doi:10.1242/dmm.002873 · Cited by 42 · see citing works
Vendramini, S., Richieri-Costa, A., & Guion-Almeida, M. (2007) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201770 · Cited by 43
Ma, Y.-P., Li, D.-W., Chai, L., Luciani, A., Ford, D., Morgan, J., & Maizel, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106468200 · Cited by 42 · see citing works
Molecular cloning, chromosomal localization, and expression of the murine SALL1 ortholog Sall1
Buck, A., Archangelo, L., Dixkens, C., & Kohlhase, J. (2000) · Cytogenetic and Genome Research · doi:10.1159/000015598 · Cited by 42 · see citing works
“In order to identify the first exon of the isolated gene, the cosmid clone was restriction digested and hybridized at reduced stringency conditions with a SALL1 PCR fragment containing exon 1 coding sequence (Kohlhase et al., 1999).”
BackgroundMethodInfluentialSelf-citationMiyagawa, S., Harada, M., Matsumaru, D., Tanaka, K., Inoue, C., Nakahara, C., Haraguchi, R., Matsushita, S., Suzuki, K., Nakagata, N., et al. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.21 · Cited by 40 · see citing works
Al-Qattan, M. M., Abdulkareem, I. A., Alhaidan, Y., & Balwi, M. A. A. (2012) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.35584 · Cited by 39 · see citing works
Unique family with Townes-Brocks syndrome, SALL1 mutation, and cardiac defects.
Surka, W., Kohlhase, J., Neunert, C., Schneider, D., & Proud, V. (2001) · American journal of medical genetics · doi:10.1002/1096-8628(20010815)102:3 · Cited by 39 · see citing works
Self-citationStrategies for screening for hereditary non-polyposis colorectal cancer
Loukola, A., de la Chapelle, A., & Aaltonen, L. (1999) · Journal of Medical Genetics · doi:10.1136/jmg.36.11.819 · Cited by 38
Keegan, C., Mulliken, J., Wu, B.-L., & Korf, B. (2001) · Genetics in Medicine · doi:10.1097/00125817-200107000-00007 · Cited by 37
Townes-Brocks syndrome and renal dysplasia: a novel mutation in the SALL1 gene
Salerno, A., Kohlhase, J., & Kaplan, B. S. (2000) · Pediatric nephrology (Berlin, West) · doi:10.1007/s004670050006 · Cited by 37 · see citing works
Self-citationAlternative splicing in aging and age-related diseases
Li, H., Wang, Z., Ma, T., Wei, G., & Ni, T. (2017) · Translational Medicine of Aging · doi:10.1016/j.tma.2017.09.005 · Cited by 39 · see citing works
The Role of Stem Cell Factor SALL4 in Leukemogenesis
Gao, C., Kong, N. R., & Chai, L. (2011) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.v16.i1-2.110 · Cited by 32 · see citing works
Identification of 2.3-Mb Gene Locus for Congenital Aural Atresia in 18q22.3 Deletion
Dostal, A., Němečková, J., Gaillyová, R., Vranová, V., Žežulková, D., Lejska, M., Šlapák, I., Dostálová, Z., & Kuglík, P. (2006) · Otology & Neurotology · doi:10.1097/00129492-200604000-00022 · Cited by 32 · see citing works
“Syndromes associated with the CAA phenotype include Treacher-Collins syndrome (6), branchio-oto-renal syndrome (7), TeunissenCremers syndrome (8), Townes-Brocks syndrome (9), and Crouzon syndrome (10).”
BackgroundMiller, E., Hopkin, R., Bao, L., & Ware, S. (2012) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.34426 · Cited by 34 · see citing works
Promoter methylation of the SALL2 tumor suppressor gene in ovarian cancers
Sung, C. K., Li, D., Andrews, E. H., Drapkin, R., & Benjamin, T. L. (2012) · Molecular Oncology · doi:10.1016/j.molonc.2012.11.005 · Cited by 32 · see citing works
Terhal, P. A., Rösler, B., & Kohlhase, J. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31060 · Cited by 26 · see citing works
“Two studies so far reported a nonsense mutation in SALL1 in one patient each with features of both Townes–Brocks syndrome and hemifacial microsomia [Kohlhase et al., 1999 (case reported by Gabrielli et al., 1993), Keegan et al., 2001].”
BackgroundSelf-citationKohlhase, J., Liebers, M., Backe, J., Baumann-Muller, A., Bembea, M., Destrėe, A., Gattas, M., Grüssner, S., Muller, T., Mortier, G., et al. (2003) · Journal of Medical Genetics · doi:10.1136/jmg.40.11.e127 · Cited by 30 · see citing works
Self-citationDefining the heterochromatin localization and repression domains of SALL1.
Netzer, C., Bohlander, S., Hinzke, M., Chen, Y., & Kohlhase, J. (2006) · Biochimica et Biophysica Acta · doi:10.1016/j.bbadis.2005.12.005 · Cited by 29 · see citing works
“Our detection rate of SALL1 mutations among typical TBS patients is about 64% [3].”
BackgroundSelf-citationHomozygous SALL1 Mutation Causes a Novel Multiple Congenital Anomaly—Mental Retardation Syndrome
Vodopiutz, J., Zoller, H., Fenwick, A., Arnhold, R., Schmid, M., Prayer, D., Müller, T., Repa, A., Pollak, A., Aufricht, C., et al. (2013) · Jornal de Pediatria · doi:10.1016/j.jpeds.2012.08.042 · Cited by 28 · see citing works
“Together, the decreased amount and supposedly limited functionality of SALL1 protein initially imply loss-of-function as the disease mechanism in CNS-TBS.”
BackgroundInfluentialChai, L. (2011) · Transfusion · doi:10.1111/j.1537-2995.2011.03371.x · Cited by 24 · see citing works
Immunoexpression of SALL4 in Wilms Tumors and Developing Kidney
Deisch, J. K., Raisanen, J. M., & Rakheja, D. (2011) · Pathology & Oncology Research · doi:10.1007/s12253-011-9364-0 · Cited by 29 · see citing works
“The renal malformations include hypoplastic or dysplastic kidneys, renal agenesis, and multicystic kidneys [5, 6].”
BackgroundThe multifaceted links between hearing loss and chronic kidney disease
Greenberg, D., Rosenblum, N. D., & Tonelli, M. (2024) · Nature Reviews Nephrology · doi:10.1038/s41581-024-00808-2 · Cited by 26
“Central clinical features include anorectal, hand, foot, and outer ear anomalies, accompanied by conductive, sensorineural, or mixed hearing loss 106 .”
Kosaki, R., Fujimaru, R., Samejima, H., Yamada, H., Izumi, K., Iijima, K., & Kosaki, K. (2007) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.31700 · Cited by 26 · see citing works
Aberrant hypomethylation of SALL4 gene in patients with myelodysplastic syndrome
Lin, J., Qian, J., Yao, D., Qian, W., Yang, J. C., Wang, C., Chai, H., Ma, J., Deng, Z., Li, Y., et al. (2012) · Leukemia Research · doi:10.1016/j.leukres.2012.10.014 · Cited by 23 · see citing works
“[3] Kohlhase J, Taschner P, Burfeind P, Pasche B, Newman B, Blanck C, et al.”
BackgroundHsal 1 is related to kidney and gonad development and is expressed in Wilms tumor
Ma, Y., Singer, D. B., Gozman, A., Ford, D., Chai, L., Steinhoff, M. M., Hansen, K., & Maizel, A. (2001) · Pediatric Nephrology · doi:10.1007/s004670100624 · Cited by 25 · see citing works
“The human homologue of the Drosophila Sal gene, Hsal 1, maps to chromosome 16q12.1, where alterations of this locus were found in TBS families [1, 3, 7]. All mutations identified so far [ 3 , 8] suggest that TBS is a dominant developmental disease resulting from Hsal 1 haploinsufficiency.”
InfluentialGenome-wide scanning reveals complex etiology of oculo-auriculo-vertebral spectrum.
Huang, X.-S., Li, X., Tan, C., Xiao, L., Jiang, H.-O., Zhang, S.-F., Wang, D., & Zhang, J.-X. (2010) · Tohoku journal of experimental medicine · doi:10.1620/tjem.222.311 · Cited by 22
Atypical phenotype and intrafamilial variability associated with a novel SALL1 mutation
Albrecht, B., Liebers, M., & Kohlhase, J. (2004) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.20484 · Cited by 22 · see citing works
“…to the region encoding the first double zinc-finger domain, seemed rather specific, since most of the TBS patients in whom mutations were detected, showed at least two of three major criteria for TBS, that is, malformations of the thumbs, ears, or anus [Kohlhase et al., 1999; Marlin et al., 1999].”
BackgroundSelf-citationDysplasies oto-mandibulaires : génétique et nomenclature des formes syndromiques
Burglen, L., Soupre, V., Diner, P., Gonzales, M., & Vazquez, M. (2001) · doi:10.1016/s0294-1260(01)00054-1 · Cited by 21
The Polyoma Virus Large T Binding Protein p150 Is a Transcriptional Repressor of c-MYC
Sung, C. K., Yim, H., Gu, H., Li, D., Andrews, E. H., Duraisamy, S., Li, C., Drapkin, R., & Benjamin, T. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046486 · Cited by 20 · see citing works
“Evolutionarily conserved SALL genes encode multi-zinc finger transcription factors that function in embryonic development in invertebrate and vertebrate species [4] including man [5,6,7,8].”
BackgroundWieczorek, D., Shaw-Smith, C., Kohlhase, J., Schmitt, W., Buiting, K., Coffey, A., Howard, E., Hehr, U., & Gillessen-kaesbach, G. (2007) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.31752 · Cited by 20
Self-citationInheritance of Chiari-Like Malformation: Can a Mixed Breeding Reduce the Risk of Syringomyelia?
Knowler, S. P., van den Berg, H., McFadyen, A. K., Ragione, R. M. L., & Rusbridge, C. (2016) · PLoS ONE · doi:10.1371/journal.pone.0151280 · Cited by 18 · see citing works
“Another, the diameter of a ‘best fit occipital lobe circle’ (f-diameter) is strongly associated with a genomic region on CFA2 containing a single candidate gene, Sall-1, [30] mutations of which are involved with branchial arch development and can be associated with Chiari type I malformation in human (Townes-Brocks sy…”
BackgroundFaguer, S., Pillet, A., Chassaing, N., Merhenberger, M., Bernadet-Monrozies, P., Guitard, J., & Chauveau, D. (2008) · Nephrology, Dialysis and Transplantation · doi:10.1093/ndt/gfp014 · Cited by 19
“In addition, germline mosaı̈cism has been proven in two unrelated cases [15,29].”
BackgroundInfluentialExpression of csal1 in pre limb-bud chick embryos
Sweetman, D., Smith, T. G., Farrell, E. R., & Münsterberg, A. (2005) · The International Journal of Developmental Biology · doi:10.1387/ijdb.051985ds · Cited by 13 · see citing works
Optic cup morphogenesis across species and related inborn human eye defects
Cardozo, M. J., Sánchez-Bustamante, E., & Bovolenta, P. (2023) · Development · doi:10.1242/dev.200399 · Cited by 26 · see citing works
Böhm, J., Munk‐Schulenburg, S., Felscher, S., & Kohlhase, J. (2006) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.31383 · Cited by 19 · see citing works
Self-citationKidney development conserved over species: essential roles of Sall1
Nishinakamura, R. (2003) · Seminars in Cell and Developmental Biology · doi:10.1016/s1084-9521(03)00027-2 · Cited by 16 · see citing works
Liberalesso, P., Cordeiro, M. L., Karuta, S., Koladicz, K., Nitsche, A., Zeigelboim, B., Raskin, S., & Rauchman, M. (2017) · BMC Medical Genetics · doi:10.1186/s12881-017-0483-7 · Cited by 17
“palate, lip, and mandible as well as the absence, in most cases, of upper limb or anal malformations, overlapping toes, and hypospadias [9].”
BackgroundSung, C. K., Dahl, J., Yim, H., Rodig, S. J., & Benjamin, A. T. L. (2011) · The FASEB Journal · doi:10.1096/fj.10-173674 · Cited by 18 · see citing works
Barry, J. S., & Reddy, M. A. (2008) · Ophthalmic Genetics · doi:10.1080/13816810802354224 · Cited by 16 · see citing works
Kidney failure in Townes–Brocks syndrome: An under recognized phenomenon?
Reardon, W., Casserly, L., Birkenhäger, R., & Kohlhase, J. (2007) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.31699 · Cited by 16
Self-citationNo evidence of SALL4‐mutations in isolated sporadic duane retraction “syndrome” (DURS)
Wabbels, B., Lorenz, B., & Kohlhase, J. (2004) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30321 · Cited by 16 · see citing works
Self-citationFrom ureteric bud to the first glomeruli: genes, mediators, kidney alterations
Fanos, V., Loddo, C., Puddu, M., Gerosa, C., Fanni, D., Ottonello, G., & Faa, G. (2014) · International Urology and Nephrology · doi:10.1007/s11255-014-0784-0 · Cited by 16 · see citing works
Beaudoux, O., Lèbre, A., Doco-Fenzy, M., Spodenkiewicz, M., Canivet, E., Colosio, C., & Poirsier, C. (2021) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.62050 · Cited by 14 · see citing works
“…confirmation have been reported in the medical literature (Botzenhart et al., 2005, 2007; Choi et al., 2010; Engels et al., 2000; Faguer et al., 2009; Kohlhase et al., 1998, 1999; Miller et al., 2012; Rodríguez Asensio et al., 2003; Sudo et al., 2010; Surka et al., 2001; Walter et al., 2006).”
BackgroundReview of Preferential Suspicious Genes in Microtia Patients Through Various Approaches.
Lu, M., Lu, X.-S., Jiang, H.-Y., & Pan, B. (2020) · The Journal of craniofacial surgery (Print) · doi:10.1097/scs.0000000000006244 · Cited by 14 · see citing works
“PATHOGENETIC GENE STUDIES OF SYNDROMES WITH MICROTIA Microtia can occur as an isolated birth defect,(16,17) but about 40% patients present with other structural abnormalities as a syndrome, such as cardiovascular, urinary and other craniofacial system defects, some of which are well-established human singlegene disord…”
BackgroundLiang, Y., Shen, D.-H., & Cai, W. (2008) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2007.09.079 · Cited by 14
“Therefore, it is predicted that mutations lead to a preterminal stop codon and produce a truncated SALL1 protein lacking all 4 double zinc finger domains [9,10].”
BackgroundMethodInfluentialGoodin, K., Prucka, S., Woolley, A., Kohlhase, J., Smith, R. J. H., Grant, J., & Robin, N. (2009) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.32673 · Cited by 13
“SALL1 mutation analysis was performed by direct sequencing of the complete coding region and deletion analysis by quantitative Real Time PCR as described [Kohlhase et al., 1999; Borozdin et al., 2006].”
BackgroundMethodSelf-citationFang, M., Zhang, X., Cao, Y., Wang, Y., & Zhang, X. (2017) · BMC Cancer · doi:10.1186/s12885-017-3843-y · Cited by 13 · see citing works
“Mutations in SALL1 cause Townes–Brocks syndrome, which is associated with several developmental defects [20].”
Transcription factors that define the epigenome structures and transcriptomes in microglia
Saeki, K., & Ozato, K. (2025) · Experimental Hematology · doi:10.1016/j.exphem.2025.104814 · Cited by 11 · see citing works
Lin, F.-J., Lu, W., Gale, D., Yao, Y., Zou, R.-J., Bian, F., & Jiang, G. (2016) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2016.3035 · Cited by 9 · see citing works
“It is also possible that one of the parents carries the mutation in a mosaic state, as germline mosaicism in clinically unaffected parents has been reported in TBS cases (11).”
The tumor suppressor protein p150Sal2 in carcinogenesis
Sung, C. K., & Yim, H. (2015) · Tumor Biology · doi:10.1007/s13277-014-3019-1 · Cited by 8 · see citing works
“Mutations in SALL1 lead to Townes-Brocks syndrome, which is associated with a variety of developmental defects [3], whereas mutations in SALL4 result in Okihiro syndromewith defects in heart and kidney development [4, 5].”
BackgroundPrenatal diagnosis of Smith-Lemli-Opitz syndrome by mutation analysis
Bzd�ch, V., Koz�k, L., Francová, H., & Beh�lov�, D. (2000) · American Journal of Medical Genetics · doi:10.1002/1096-8628(20001106)95:1 · Cited by 9 · see citing works
Townes-Brocks Syndrome Revealed by Kidney Gene Panel Testing
Stein, Q., Vostrizansky, A., Magay, Y., Jandeska, S., Westemeyer, M., Hendricks, E., Pitman, T., Hager, M., Anand, A., Curry, K., et al. (2024) · Kidney International Reports · doi:10.1016/j.ekir.2024.03.030 · Cited by 8 · see citing works
“7,11,13,25,26 However, todate no genotype-phenotype correlations have been established for the majority of P variants.”
Yan, X.-H., Wang, J., Yang, W., Li, L.-K., Shen, T., Geng, J., Zhang, Q., Zhong, M., Xiong, W.-Y., Bu, F.-X., et al. (2024) · Journal of Medical Genetics · doi:10.1136/jmg-2023-109579 · Cited by 8 · see citing works
“26 And for the 11 patients who got diagnosed during or after early adolescence (≥12 years old), 4 out of 11 suffered from ESRD at the time of evaluation 27–30 (online supplemental table 5).”
BackgroundOcular manifestations of congenital anomalies of the kidney and urinary tract (CAKUT)
Virth, J., Mack, H., Colville, D., Crockett, E., & Savige, J. (2023) · Pediatric nephrology (Berlin, West) · doi:10.1007/s00467-023-06068-9 · Cited by 8
Shared features in ear and kidney development – implications for oto-renal syndromes
Wang, S. X., & Streit, A. (2024) · Disease Models & Mechanisms · doi:10.1242/dmm.050447 · Cited by 7 · see citing works
Pérez-Cabrera, A., Kofman-Alfaro, S., & Zenteno, J. (2002) · Journal of Orthopaedic Research · doi:10.1016/s0736-0266(02)00008-6 · Cited by 7
Innoceta, A. M., Olivucci, G., Parmeggiani, G., Scarano, E., Pragliola, A., & Graziano, C. (2023) · Genes · doi:10.3390/genes14020258 · Cited by 7 · see citing works
“[19] 3-1 + + + + + − − + 4-1 + + + + + − + − 5-1 − + + + + + + −”
Clinical characteristics of patients with SALL1-related disorder
Asagai, Y., Tanaka, Y., Hanafusa, H., Nagano, C., Horinouchi, T., Ishimori, S., Kaito, H., Iijima, K., Nozu, K., & Morisada, N. (2025) · Pediatric nephrology (Berlin, West) · doi:10.1007/s00467-025-06878-z · Cited by 6 · see citing works
“We conducted direct sequencing, multiplex ligation-dependent probe amplification (MLPA), array comparative genomic hybridization (aCGH), and targeted sequencing of genes associated with inherited disease using NGS. Direct sequencing was performed as previously described [10].”
Wang, Z., Sun, Z., Diao, Y., Wang, Z.-Y., Yang, X.-D., Jiang, B., Wu, Y.-M., & Liu, G.-Y. (2023) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-023-02874-4 · Cited by 6 · see citing works
“The patients with SALL1 mutations (c.419delC) have similar symptoms such as external ear dysplasia, finger deformity and renal function impaired [15].”
BackgroundSills, E. S., & Wood, S. H. (2021) · Global Medical Genetics · doi:10.1055/s-0041-1740018 · Cited by 6 · see citing works
Endocrine Abnormalities in Townes–Brocks Syndrome
Lawrence, C., Hong-McAtee, I., Hall, B., Hartsfield, J., Rutherford, A., Bonilla, T., & Bay, C. (2013) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.36104 · Cited by 6
“Endocrine abnormalities have rarely been associated with TBS, with only three previously documented cases of hypothyroidism and a proven SALL1 mutation [Kohlhase et al., 1999; Botzenhart et al., 2005; Choi et al., 2010].”
BackgroundInfluentialvan den Akker, P. C., van de Graaf, R., Dooijes, D., & van Essen, A. J. (2009) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.32738 · Cited by 8 · see citing works
Mosaic trisomy 8 and Townes–Brocks syndrome due to a novel SALL1 mutation in the same patient
Walter, K., Greenhalgh, K., Newbury-Ecob, R., & Kohlhase, J. (2006) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.31136 · Cited by 6 · see citing works
“Since the hypothetical truncated Q927X protein will contain more zinc finger domains than truncated proteins resulting from SALL1mutations in the ‘‘hotspot’’ region of exon 2 [Kohlhase et al., 1999], it might have a preserved residual function thereby causing a rather mild phenotype.”
BackgroundSelf-citationTownes-Brocks syndrome with craniosynostosis in two siblings
Lugli, L., Rossi, C., Ceccarelli, P. L., Calabrese, O., Bedetti, L., Miselli, F., Bianchini, M. A., Iughetti, L., & Berardi, A. (2022) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2022.104642 · Cited by 5 · see citing works
Autosomal Dominant Tubulointerstitial Kidney Disease: A Review.
Bleyer, A., Kidd, K., Živná, M., & Kmoch, S. (2025) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2025.05.015 · Cited by 5
van Bever, Y., Gischler, S., Hoeve, H., Smit, L., Nauta, J., & Dooijes, D. (2009) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2009.09.001 · Cited by 5
McCann, E., Fryer, A. E., Newman, W. N., Appleton, R. E., & Kohlhase, J. (2005) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.30962 · Cited by 6 · see citing works
“1 [Kohlhase et al., 1999].”
Self-citationDemir, Y., Samli, H., Yucel, A., Yılmaz, M., Haktanir, N. T., Maralcan, G., & Solak, M. (2006) · American Journal of Medical Genetics. Part A · doi:10.1002/ajmg.a.31147 · Cited by 4
Wabbels, B., Kohlhase, J., & Lorenz, B. (2004) · doi:10.1055/s-2004-813662 · Cited by 4
Self-citationAbsent Optic Chiasm Presenting With Horizontal Nystagmus
Salchow, D., Kohlhase, J., Miller, M., Kadom, N., FitzGibbon, E., Caruso, R., & Brooks, B. (2010) · Journal of pediatric ophthalmology and strabismus · doi:10.3928/01913913-20090818-08 · Cited by 3
Self-citation
- Authors
- Kohlhase, J., Taschner, P. E. M., Burfeind, P., Pasche, B., Newman, B., Blanck, C., Breuning, M. H., ten Kate, L. P., Maaswinkel-Mooy, P., Mitulla, B., Seidel, J., Kirkpatrick, S. J., Pauli, R. M., Wargowski, D. S., Devriendt, K., Proesmans, W., Gabrielli, O., Coppa, G. V., Wesby–van Swaay, E., Trembath, R. C., Schinzel, A. A., Reardon, W., Seemanova, E., & Engel, W.
- Affiliations
- University of Göttingen (DE)
- Leiden University (NL)
- Leiden University Medical Center (NL)
- Jena University Hospital (DE)
- University of Wisconsin–Madison (US)
- KU Leuven (BE)
- Leicester Royal Infirmary (GB)
- University of Zurich (CH)
- University College London (GB)
- Corresponding author
- Kohlhase, Jürgen
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 64
- Issue
- 2
- Pages
- 435-445
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1377753
- OpenAlex
- W1975829825
- Cited by
- 152
- References
- 0
- Citations by year
- 2025: 5 · 2024: 5 · 2023: 6 · 2022: 3 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 6
- FWCI
- 9.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- Townes-Brocks syndrome, SALL1, zinc finger transcription factor, genotype-phenotype correlation, nonsense mutation, Goldenhar syndrome, renal anomalies, ear anomalies, limb malformations
- MeSH terms
- Abnormalities, Multiple, Anus, Imperforate, Base Sequence, Cloning, Molecular, Exons, Female, Hearing Loss, Sensorineural, Humans, Male, Molecular Sequence Data, Mutation, Pedigree, Polymorphism, Genetic, Syndrome, Transcription Factors, Zinc Fingers, Frameshift Mutation
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