Cited by 160Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

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Steroid 21-hydroxylase deficiency: two additional mutations in salt-wasting disease and rapid screening of disease-causing mutations

Wedell, Anna, Luthman, Holger·1993·Human Molecular Genetics

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Abstract

A method for genetic diagnosis of steroid 21-hydroxylase deficiency was developed based on allele-specific PCR. With this approach, genotyping of fourteen mutations and diagnosis of homozygous gene deletions can be performed within hours from tissue sampling. One patient with salt-wasting disease had normal genotype at all positions screened. DNA sequencing revealed two novel mutations, a G to C transversion at the conserved splice donor site of intron 7 and a TGG to TAG nonsense mutation at Trp 406 in exon 9. Allele-specific PCR was established also for these mutations and used to screen for their presence in the pseudogene. However, the two novel mutations were not found in at least 34 pseudogenes.

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Background
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Self-citation
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Self-citation
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Self-citation
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“In addition to these technical difficulties in mutation detection, discrepancies in genotype-phenotype correlation may result from de novo conversions, more than one partially inactivating mutation on a single allele, or unique singlefamily mutations, whose frequency does not seem to be negligible (7, 10, 11, 23, 26).”
BackgroundMethod
Mutations in steroid 21-hydroxylase (CYP21)
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“The sequences selected for specificity were: the normal counterparts of the 8-bp deletion (del8bp) in exon 3 (Owerbach et al. 1990; Tusie-Luna et al. 1991; Wedell and Luthman 1993) or codons 236-239 in exon 6 that differentiate CYP21B from CYP21A by four deoxynucleotides (Owerbach et al.”
Background
EMQN best practice guidelines for molecular genetic testing and reporting of 21-hydroxylase deficiency
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Method
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“The nucleotide positions are as described in the Human Gene Mutation Base (Cardiff, UK), and the PCR methodology is adapted from that of Wedell and Luthman (26).”
Method
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MethodSelf-citation
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CONGENITAL ADRENAL HYPERPLASIA
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“Allele-speci®c PCR methodology described by Wedell & Luthman (1993) was used for the identi®cation of rare mutations as: Ins T, G291S, I7 splice, W405X, P453S, R483P and R483!frameshift mutations.”
Method
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Method
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“Downloaded from jcem.endojournals.org by on February 2, 2010 method proposed by Wedel and Luthman was followed with slight modifications ( 13 ).”
Method
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Self-citation
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Method
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Self-citation
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de Carvalho, D. F., Miranda, M. C., Gomes, L. G., Madureira, G., Marcondes, J. A. M., Billerbeck, A. E. C., Rodrigues, A. S., Presti, P. F., Kuperman, H., Damiani, D., et al. (2016) · European Journal of Endocrinology · doi:10.1530/eje-16-0171 · Cited by 75
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“Together with apparent gene deletions and large gene conversions, nine pseudogene-derived mutations are responsible for approximately 90 –95% of all CAH alleles ( 11 ).”
Background
Detection of Y‐specific sequences in 122 patients with Turner syndrome: Nested PCR is not a reliable method
Nishi, M. Y., Domenice, S., de Medeiros, M. A., Mendonca, B. B., & Billerbeck, A. E. C. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10168 · Cited by 72
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“a Primers from Wedell and Luthman (26).”
Method
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“Ten such rare mutations have been described so far, six of which are missense mutations (Helmberg et al. 1992; Wedell et al. 1992; Gunn et al. 1993; Wedell and Luthman 1993 a, b; Lajic and Wedell 1996; Levo and Partanen 1997 a). We here describe two additional missense mutations, one found in a Swedish patient origina…”
BackgroundMethodInfluentialSelf-citation
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“A mutation in the adjacent nucleotide 1784 was identified in a Swedish patient carrying the salt-wasting phenotype (Wedell and Luthman 1993b).”
Background
Three Novel Mutations in CYP21 Gene in Brazilian Patients with the Classical Form of 21-Hydroxylase Deficiency Due to a Founder Effect
Billerbeck, A. E. C., Mendonca, B. B., Pinto, E. M., Madureira, G., Arnhold, I. J. P., & Bachega, T. A. S. S. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2001-011939 · Cited by 65
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Self-citation
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“Determination of the known pseudogene-derived mutations in CYP21 (White et al. 1994) was performed using gene-specific PCR amplification followed by mutation-specific PCR (a local modification of the method described in Wedell and Luthman 1993b ), direct DNA sequencing, or PCR/RFLP.”
Method
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Dracopoulou, M., Maniati-Christidi, M., & Dacou‐Voutetakis, C. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.6.7574 · Cited by 66
“Allele-specific PCR was employed, as previously described by A. Wedell and H. Luthman ( 8 ), to identify the following molecular defects of the CYP21 gene: P30L (exon 1); I2 splice (intron 2); 8bpdE3 (exon 3); I172N (exon 4); clusterE6 (exon 6); V281L, G291S, and F3061T (exon 7); Q318stop and R356W (exon 8); and P453S…”
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“By typing for nine pseudogene-derived mutations by allelespecific PCR, approximately 95% of all mutated CYP21 alleles are detected ( 11 ).”
BackgroundMethodSelf-citation
Congenital adrenal hyperplasia: focus on the molecular basis of 21-hydroxylase deficiency
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Self-citation
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Self-citation
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Self-citation
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Paulino, L. C., Araujo, M., Guerra‐Júnior, G., Marini, S., & de Mello, M. P. (1999) · Acta Paediatrica · doi:10.1080/08035259950170024 · Cited by 49
Genetic Diseases of Steroid Metabolism
White, P. C. (1994) · Vitamins and hormones · doi:10.1016/s0083-6729(08)61147-4 · Cited by 43
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Nermoen, I., Brønstad, I., Fougner, K. J., Svartberg, J. B., Øksnes, M., Husebye, E. S., & Løvås, K. (2012) · European Journal of Endocrinology · doi:10.1530/eje-12-0196 · Cited by 43
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Miles, H. L., Gidlöf, S. B., Nordenström, A., et al. (2010) · Archives of Disease in Childhood Fetal & Neonatal · doi:10.1136/adc.2009.173575 · Cited by 41
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Self-citation
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Gunther, D. F., Bukowski, T. P., Ritzén, E. M., Wedell, A., & Wyk, J. J. V. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.10.4281 · Cited by 43
Self-citation
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Billerbeck, A. E. C., Bachega, T. A. S. S., Frazzatto, E., Nishi, M. Y., Goldberg, A. C., Marin, M. L. C., Madureira, G., Monte, O., Arnhold, I. J. P., & Mendonca, B. B. (1999) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.84.8.5937 · Cited by 44
“This specificity was achieved by using a primer located in exon 3 that does not contain the eight-nucleotide deletion specific for the pseudogene. The primers used were P4 and P55 ( 10 ).”
BackgroundMethodInfluential
Hormonal evaluation and mutation screening for steroid 21-hydroxylase deficiency in patients with unilateral and bilateral adrenal incidentalomas
Patócs, A., Tóth, M., Barta, C., Sasvári‐Székely, M., Varga, I., Szücs, N., Jakab, C., Gláz, E., & Rácz, K. (2002) · European Journal of Endocrinology · doi:10.1530/eje.0.1470349 · Cited by 38
“has been proved to detect homozygous normal, homozygous mutant or heterozygous genotypes for the eight commonly occurring mutations with the exception of heterozygous deletion (28, 29 , 44), which could result in some underestimation of the occurrence of heterozygous carriers.”
BackgroundMethod
Mutation screening in British 21-hydroxylase deficiency families and development of novel microsatellite based approaches to prenatal diagnosis
Lako, M., Ramsden, S., Campbell, R. D., & Strachan, T. (1999) · Journal of Medical Genetics · doi:10.1136/jmg.36.2.119 · Cited by 38
“Detection of CYP21 point mutations was carried out essentially as described by Wedell and Luthman.”
Salt-wasting congenital adrenal hyperplasia: Detection of mutations in CYP21B gene in a Chilean population1
Fardella, C. E., Poggi, H., Pineda, P., Soto, J., Torrealba, I., Cattani, A., Oestreicher, E., & Foradori, A. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.9.5071 · Cited by 35
An intron 1 splice mutation and a nonsense mutation (W23X) in CYP21 causing severe congenital adrenal hyperplasia
Lajić, S., & Wedell, A. (1996) · Human Genetics · doi:10.1007/s004390050186 · Cited by 32
“Nine such rare mutations have been reported to date (Wedell et al. 1992; Helmberg et al. 1992; Gunn et al. 1993; Wedell and Luthman 1993 a, b). In this communication, we describe two additional rare CYP21 mutations in two Swedish CAH patients.”
BackgroundSelf-citation
Using Real-Time, Quantitative PCR for Rapid Genotyping of the Steroid 21-Hydroxylase Gene in a North Florida Population
Olney, R. C., Mougey, E. B., Wang, J., Shulman, D. I., & Sylvester, J. E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.2.8273 · Cited by 36
“Positive control DNA for the mutations was kindly provided by Dr. Anna Wedell (Karolinska Hospital, Stockholm, Sweden) (6).”
BackgroundMethodInfluential
Molecular Diagnosis of CYP21 Mutations in Congenital Adrenal Hyperplasia
Speiser, P. (2001) · American Journal of PharmacoGenomics · doi:10.2165/00129785-200101020-00003 · Cited by 33
“[44] This technique has similar advantages to the amplification created restriction site approach; it requires more PCR reactions but does not require restriction digests.”
Method
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Lau, I. F., Soardi, F. C., de Lemos‐Marini, S. H. V., Guerra‐Júnior, G., Baptista, M. T. M., & de Mello, M. P. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.12.8113 · Cited by 33
Molecular analysis of CYP21A2 can optimize the follow‐up of positive results in newborn screening for congenital adrenal hyperplasia
Silveira, E., Elnecave, R., Dos Santos, E., Moura, V, Pinto, E., Van Der Linden Nader, I., Mendonca, B., & Bachega, T. (2009) · Clinical Genetics · doi:10.1111/j.1399-0004.2009.01274.x · Cited by 31
“entire CYP21A2 gene, including the promoter region, was PCR amplified with specific primers, and the products were submitted to direct sequencing, as previously described (10, 15).”
Method
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Minutolo, C., Nadra, A. D., Fernández, C. S., Taboas, M., Buzzalino, N. D., Casali, B., Belli, S., Charreau, E. H., Alba, L. G., & Daín, L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0015899 · Cited by 33
In vitro functional studies of rare CYP 21A2 mutations and establishment of an activity gradient for nonclassic mutations improve phenotype predictions in congenital adrenal hyperplasia
Barbaro, M., Soardi, F. C., Östberg, L. J., Persson, B., de Mello, M. P., Wedell, A., & Lajić, S. (2014) · Clinical Endocrinology · doi:10.1111/cen.12526 · Cited by 31
Self-citation
Congenital Adrenal Hyperplasia: The Molecular Basis of 21-Hydroxylase Deficiency in H-2aw18 Mice
Riepe, F. G., Tatzel, S., Sippell, W. G., Pleiss, J., & Krone, N. P. (2005) · Endocrinology · doi:10.1210/en.2004-1563 · Cited by 31
Classical and nonclassical 21‐hydroxylase deficiency: a molecular study of Argentine patients
Daín, L., Buzzalino, N. D., Oneto, A., Belli, S., Stivel, M., Pasqualini, T., Minutolo, C., Charreau, E. H., & Alba, L. G. (2002) · Clinical Endocrinology · doi:10.1046/j.0300-0664.2001.01419.x · Cited by 31
“Nevertheless, alleles-specific PCRs with both mutated and normal primers in different orientations (Wedell et al., 1994b) will be performed for those patients where the cis-trans segregation of mutations have not been yet determined (see Results).”
MethodInfluential
A 31-year-old woman with infertility and polycystic ovaries diagnosed with non-classic congenital adrenal hyperplasia due to a novel CYP21 mutation
Falhammar, H., Thoren, M., & Hagenfeldt, K. (2008) · Journal of Endocrinological Investigation · doi:10.1007/bf03345586 · Cited by 30
Homozygous deletion of the CYP21A-TNXA-RP2-C4B gene region conferring C4B deficiency associated with recurrent respiratory infections
Jaatinen, T., Ruuskanen, O., Truedsson, L., & Lokki, M. (1999) · Human Immunology · doi:10.1016/s0198-8859(99)00047-6 · Cited by 29
Mutation Analysis in Patients with Congenital Adrenal Hyperplasia in the Spanish Population: Identification of Putative Novel Steroid 21-Hydroxylase Deficiency Alleles Associated with the Classic Form of the Disease
Lobato, M. N., Ordóñez-Sánchez, M. L., Tusié-Luna, M. T., & Meseguer, A. (1999) · Human Heredity · doi:10.1159/000022866 · Cited by 30
“These point mutations can lead to amino acid substitutions [6‐14], premature termination codons [15‐18], frameshift [6, 19] and mutations that affect RNA splicing [ 16 , 17, 19].”
Background
Recent advances in biochemical and molecular analysis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Choi, J. H., Kim, G.-H., & Yoo, H. (2016) · Annals of Pediatric Endocrinology & Metabolism · doi:10.6065/apem.2016.21.1.1 · Cited by 31
The Adrenal Cortex and Its Disorders
Miller, W. L., Achermann, J. C., & Flück, C. E. (2008) · Elsevier eBooks · doi:10.1016/b978-141604090-3.50017-x · Cited by 28
Genetic disorders of steroid hormone synthesis and metabolism
New, M. I., & White, P. C. (1995) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(95)80587-7 · Cited by 27
Intronic polymorphisms of cytochromes P450
Ingelman‐Sundberg, M., & Sim, S. C. (2010) · Human Genomics · doi:10.1186/1479-7364-4-6-402 · Cited by 26
No overrepresentation of congenital adrenal hyperplasia in patients with adrenocortical tumours
Kjellman, M., Holst, M., Bäckdahl, M., Larsson, C., Farnebo, L., & Wedell, A. (1999) · Clinical Endocrinology · doi:10.1046/j.1365-2265.1999.00655.x · Cited by 26
“By typing for nine pseudogene-derived mutations using allele-specific PCR, approximately 95% of all CYP21 mutations are detected (Wedell & Luthman, 1993).”
MethodSelf-citation
Molecular Defects of the CYP21A2 Gene in Greek-Cypriot Patients with Congenital Adrenal Hyperplasia
Skordis, N., Kyriakou, A., Tardy, V., Ioannou, Y. S., Varvaresou, A., Dracopoulou, M., Patsalis, P. C., Shammas, C., Neocleous, V., & Phylactou, L. A. (2010) · Hormone Research in Paediatrics · doi:10.1159/000320040 · Cited by 25
“The patients were classified in the SW form when clinical and biochemical findings of renal salt wasting were evident (virilization of external genitalia, failure to thrive, hyponatremia, hyperkalemia, high renin (PRA) values, and 17-OHP value >75 nmol/l in the first month of their lives). Severe clinical symptoms of…”
Ethnic disparity in 21-hydroxylase gene mutations identified in Pakistani congenital adrenal hyperplasia patients
Khan, A. H., Aban, M., Raza, J., Haq, N. U., Jabbar, A., & Moatter, T. (2011) · BMC Endocrine Disorders · doi:10.1186/1472-6823-11-5 · Cited by 27
“In one case neither of the fragments amplified, which may be due to homozygous gene deletion of CYP21A2 or to transfer into CYP21A2 of pseudogene sequences that include the 8 bp deletion in exon 3 [7].”
BackgroundMethod
Congenital Adrenal Hyperplasia Owing to 21-Hydroxylase Deficiency
New, M. I., Lekarev, O., Mancenido, D., Parsa, A. A., & Yuen, T. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-416006-4.00003-x · Cited by 24
Phenotypic variability of hyperandrogenemia in females heterozygous for CYP21A2 mutations
Skordis, N., Neocleous, V., Shammas, C., Phedonos, A., & Phylactou, L. (2014) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.145077 · Cited by 25
Reverse dot-blot hybridization as an improved tool for the molecular diagnosis of point mutations in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency
YANG, Y.-P., CORLEY, N., & GARCIA-HERAS, J. (2001) · Molecular Diagnosis · doi:10.2165/00066982-200106030-00007 · Cited by 13
An 88-year-old woman diagnosed with adrenal tumor and congenital adrenal hyperplasia: Connection or coincidence?
Falhammar, H., & Thoren, M. (2005) · Journal of Endocrinological Investigation · doi:10.1007/bf03347226 · Cited by 23
An Androgen Receptor Gene Mutation (E653K) in a Family with Congenital Adrenal Hyperplasia due to Steroid 21-Hydroxylase Deficiency as well as in Partial Androgen Insensitivity
Giwercman, Y. L., Nordenskjöld, A., Ritzén, E. M., Nilsson, K. O., Ivarsson, S. A., Grandell, U., & Wedell, A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.6.8518 · Cited by 22
“Genetic diagnosis of the CYP21 gene was performed by allele-specific PCR as described (20).”
Method
Detection of the Bcl I polymorphism of the glucocorticoid receptor gene by single-tube allele-specific polymerase chain reaction
Gergics, P., Patócs, A., Majnik, J., Balogh, K., Szappanos, Á., Tóth, M., & Rácz, K. (2006) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2006.04.004 · Cited by 22
Molecular pathology of 21‐hydroxylase deficiency
Strachan, T. (1994) · Journal of Inherited Metabolic Disease · doi:10.1007/bf00711358 · Cited by 20
A steroid 21-hydroxylase allele concomitantly carrying four disease-causing mutations is not uncommon in the Swedish population
Wedell, A., Xu, C. D., & Luthman, H. (1994) · Human Genetics · doi:10.1007/bf00210612 · Cited by 20
“This amplification was performed with the CYP21-specific P55/P4 fragment (Wedell and Luthman 1993b).”
BackgroundMethodInfluentialSelf-citation
Disorders of sex development: a genetic study of patients in a multidisciplinary clinic
Laino, L., Majore, S., Preziosi, N., Grammatico, B., Bernardo, C. D., Scommegna, S., Rapone, A. M., Marrocco, G., Bottillo, I., & Grammatico, P. (2014) · Endocrine Connections · doi:10.1530/ec-14-0085 · Cited by 19
Characterisation of CAH alleles with non-radioactive DNA single strand conformation polymorphism analysis of the CYP21 gene.
Bobba, A., Iolascon, A., Giannattasio, S., Albrizio, M., Sinisi, A. M., Prisco, F., Schettini, F., & Marra, E. (1997) · Journal of Medical Genetics · doi:10.1136/jmg.34.3.223 · Cited by 19
Genetic defects of the CYP21A2 gene in girls with premature adrenarche
Skordis, N., Shammas, C., Phedonos, A., Kyriakou, A., Toumba, M., Neocleous, V., & Phylactou, L. A. (2014) · Journal of Endocrinological Investigation · doi:10.1007/s40618-014-0223-1 · Cited by 17
“The primers P1-P48 [18] were used to amplify the fragment containing the −370 bp CYP21A2 promoter, the 5′ untranslated region of the CYP21A2 gene that is mainly located in the first 167 nucleotides upstream the ATG codon and the 3′ untranslated region that is 536 nucleotides downstream the TGA stop codon of the CYP21A…”
Method
CYP21A2 intronic variants causing 21-hydroxylase deficiency
Concolino, P., Rizza, R., Costella, A., Carrozza, C., Zuppi, C., & Capoluongo, E. (2017) · Metabolism · doi:10.1016/j.metabol.2017.03.003 · Cited by 16
Mutations in the gene encoding 21-hydroxylase detected by solid-phase minisequencing
Ohlsson, G., & Schwartz, M. (1996) · Human Genetics · doi:10.1007/s004390050319 · Cited by 17
21-hydroxylase deficiency in Italy: a distinct distribution pattern ofCYP21 mutations in a sample from southern Italy
Bobba, A., Marra, E., Giannattasio, S., Iolascon, A., Monno, F., & MAIO, S. D. (1999) · Journal of Medical Genetics · doi:10.1136/jmg.36.8.648 · Cited by 17
Genotype Is Associated to the Degree of Virilization in Patients With Classic Congenital Adrenal Hyperplasia
Neocleous, V., Fanis, P., Phylactou, L. A., & Skordis, N. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00733 · Cited by 16
“For the amplification of the 5 untranslated region which is located in the first 167 nucleotides upstream of the ATG codon of the CYP21A2 gene, the primers P1-P48 (23) were used to amplify a fragment of 370 bp.”
Method
Effects of Missense Mutations and Deletions on Membrane Anchoring and Enzyme Function of Human Steroid 21-Hydroxylase (P450c21)
Lajić, S., Nikoshkov, A., Holst, M., & Wedell, A. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0482 · Cited by 16
Self-citation
Multiple transcripts of the CYP21 gene are generated by the mutation of the splicing donor site in intron 2 from GT to AT in 21-hydroxylase deficiency
Lee, H., & Sf, C. (2001) · Journal of Endocrinology · doi:10.1677/joe.0.1710397 · Cited by 16
“The AG to GG mutation at the splicing acceptor site in intron 1 (Lajic & Wedell 1996) and the GT to CT mutation at the donor site in intron 7 (Wedell & Luthman 1993) both disrupt the canonical consensus sequences which are crucial for splicing processing.”
Background
Mutations in fibrillar collagens (types I, II, III, and XI), fibril-associated collagen (type IX), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage, and blood vessels
Kuivaniemi, H., Tromp, G., & Prockop, D. J. (1997) · Human Mutation · doi:10.1002/(sici)1098-1004(1997)9:4 · Cited by 371
Long-read Amplicon Sequencing of the CYP21A2 in 48 Thai Patients With Steroid 21-Hydroxylase Deficiency
Tantirukdham, N., Sahakitrungruang, T., Chaisiwamongkol, R., Pongpanich, M., Srichomthong, C., Assawapitaksakul, A., Buasong, A., Tongkobpetch, S., Yeetong, P., & Shotelersuk, V. (2022) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgac187 · Cited by 14
Identification of CYP21A2 mutant alleles in Czech patients with 21-hydroxylase deficiency
Fajkusová (2010) · International Journal of Molecular Medicine · doi:10.3892/ijmm_00000504 · Cited by 15
Molecular Approaches for the Diagnosis of 21-Hydroxylase Deficiency and Congenital Adrenal Hyperplasia
Wedell, A. (1996) · Clinics in Laboratory Medicine · doi:10.1016/s0272-2712(18)30291-9 · Cited by 15
Self-citation
Rare mutations in the CYP21A2 gene detected in congenital adrenal hyperplasia
Neocleous, V., Ioannou, Y. S., Bartsota, M., Costi, C., Skordis, N., & Phylactou, L. A. (2009) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2009.05.015 · Cited by 14
“[8].”
MethodInfluential
Functional studies of novel CYP21A2 mutations detected in Norwegian patients with congenital adrenal hyperplasia
Brønstad, I., Breivik, L., Methlie, P., Wolff, A. S. B., Bratland, E., Nermoen, I., Løvås, K., & Husebye, E. S. (2014) · Endocrine Connections · doi:10.1530/ec-14-0032 · Cited by 15

Authors: Wedell, A., & Luthman, H.
Affiliations: Karolinska University Hospital (SE)
Corresponding author: Luthman, Holger
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 1993
Volume: 2
Issue: 5
Pages: 499-504
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/2.5.499
OpenAlex: W2062953189
Cited by: 160
References: 0
Citations by year: 2026: 1 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 3 · 2014: 7 · 2013: 3 · 2012: 3
FWCI: 1.93
Type: journal article
Language: en
Open access: closed
Locations: Human Molecular Genetics (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: Vetenskapsrådet
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords: 21-hydroxylase deficiency, CYP21, novel mutations, splice donor site mutation, nonsense mutation, allele-specific PCR, genetic diagnosis, congenital adrenal hyperplasia
MeSH terms: Adrenal Hyperplasia, Congenital, Alleles, Base Sequence, DNA, Female, Genotype, Humans, Molecular Sequence Data, Pseudogenes, Sodium Chloride, Steroid 21-Hydroxylase, DNA Probes, Polymerase Chain Reaction, Point Mutation

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Steroid 21-hydroxylase deficiency: two additional mutations in salt-wasting disease and rapid screening of disease-causing mutations

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