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Cited by 175Genomics and Rare DiseasesGenetics and Neurodevelopmental DisordersGenomic variations and chromosomal abnormalities

Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families

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Harripaul, R, Vasli, N, Mikhailov, A, Rafiq, M A, Mittal, K, Windpassinger, C, Sheikh, T I, Noor, A +24 more·2018·Molecular Psychiatry
DOI 10.1038/mp.2017.60

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Abstract

Approximately 1% of the global population is affected by intellectual disability (ID), and the majority receive no molecular diagnosis. Previous studies have indicated high levels of genetic heterogeneity, with estimates of more than 2500 autosomal ID genes, the majority of which are autosomal recessive (AR). Here, we combined microarray genotyping, homozygosity-by-descent (HBD) mapping, copy number variation (CNV) analysis, and whole exome sequencing (WES) to identify disease genes/mutations in 192 multiplex Pakistani and Iranian consanguineous families with non-syndromic ID. We identified definite or candidate mutations (or CNVs) in 51% of families in 72 different genes, including 26 not previously reported for ARID. The new ARID genes include nine with loss-of-function mutations (ABI2, MAPK8, MPDZ, PIDD1, SLAIN1, TBC1D23, TRAPPC6B, UBA7 and USP44), and missense mutations include the first reports of variants in BDNF or TET1 associated with ID. The genes identified also showed overlap with de novo gene sets for other neuropsychiatric disorders. Transcriptional studies showed prominent expression in the prenatal brain. The high yield of AR mutations for ID indicated that this approach has excellent clinical potential and should inform clinical diagnostics, including clinical whole exome and genome sequencing, for populations in which consanguinity is common. As with other AR disorders, the relevance will also apply to outbred populations.

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  • A homozygous loss-of-function mutation p.Arg132Ter in ABI2 was identified in a cohort of 192 multiplex Pakistani and Iranian consanguineous families.

    “Furthermore, a homozygous LoF mutation, p.Arg132Ter, in ABI2 was identified through a combination of microarray genotyping, homozygosity-by-descent (HBD) mapping, CNV analysis, and exome sequencing. This discovery was made within a cohort of 192 multiplex Pakistani and Iranian consanguineous families.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [140]

  • ABI2 is one of 26 newly identified candidate genes associated with autosomal recessive non-syndromic intellectual disability.

    “ABI2 is one of the 26 newly identified candidate genes associated with autosomal recessive non-syndromic ID140 (Table 2x).”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [140]

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Research works printed but not linked: 76

  1. Maulik PK, Mascarenhas MN, Mathers CD, Dua T, Saxena S. Prevalence of intellectual disability: a meta-analysis of population-based studies. Research in developmental disabilities 2011; 32(2): 419-436.
  2. Ropers H-H, Hamel BC. X-linked mental retardation. Nature Reviews Genetics 2005; 6(1): 46-57.
  3. de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T et al. Diagnostic exome sequencing in persons with severe intellectual disability. New England Journal of Medicine 2012; 367(20): 1921-1929.
  4. Musante L, Ropers HH. Genetics of recessive cognitive disorders. Trends in Genetics 2014; 30(1): 32-39.
  5. Rauch A, Hoyer J, Guth S, Zweier C, Kraus C, Becker C et al. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. American journal of medical genetics Part A 2006; 140(19): 2063-2074.
  6. Heslop P, Blair PS, Fleming P, Hoghton M, Marriott A, Russ L. The Confidential Inquiry into premature deaths of people with intellectual disabilities in the UK: a population-based study. The Lancet 2014; 383(9920): 889-895.
  7. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. New England Journal of Medicine 2013; 369(16): 1502-1511.
  8. Najmabadi H, Hu H, Garshasbi M, Zemojtel T, Abedini SS, Chen W et al. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature 2011; 478(7367): 57-63.
  9. Mir A, Kaufman L, Noor A, Motazacker MM, Jamil T, Azam M et al. Identification of mutations in TRAPPC9, which encodes the NIK-and IKK-β-binding protein, in nonsyndromic autosomal- recessive mental retardation. The American Journal of Human Genetics 2009; 85(6): 909-915.
  10. Rafiq MA, Kuss AW, Puettmann L, Noor A, Ramiah A, Ali G et al. Mutations in the alpha 1, 2- mannosidase gene, MAN1B1, cause autosomal-recessive intellectual disability. The American Journal of Human Genetics 2011; 89(1): 176-182.
  11. Bernkopf M, Webersinke G, Tongsook C, Koyani CN, Rafiq MA, Ayaz M et al. Disruption of the methyltransferase-like 23 gene METTL23 causes mild autosomal recessive intellectual disability. Human molecular genetics 2014; 23(15): 4015-4023.
  12. Law R, Dixon-Salazar T, Jerber J, Cai N, Abbasi AA, Zaki MS et al. Biallelic truncating mutations in FMN2, encoding the actin-regulatory protein formin 2, cause nonsyndromic autosomal-recessive intellectual disability. The American Journal of Human Genetics 2014; 95(6): 721-728.
  13. Ahmed I, Buchert R, Zhou M, Jiao X, Mittal K, Sheikh TI et al. Mutations in DCPS and EDC3 in autosomal recessive intellectual disability indicate a crucial role for mRNA decapping in neurodevelopment. Human molecular genetics 2015; 24(11): 3172-3180.
  14. Heidari A, Tongsook C, Najafipour R, Musante L, Vasli N, Garshasbi M et al. Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability. Human molecular genetics 2015; 24(20): 5697-5710.
  15. Modell B, Darr A. Genetic counselling and customary consanguineous marriage. Nature Reviews Genetics 2002; 3(3): 225-229.
  16. Hamamy H. Consanguineous marriages. Journal of community genetics 2012; 3(3): 185-192.
  17. Saadat M. Consanguinity associated with child and adult mortality in 24 Asian and African countries, an ecological study. Iranian Journal of Public Health 2007; 36: 35-39.
  18. Hussain R, Bittles A. The prevalence and demographic characteristics of consanguineous marriages in Pakistan. Journal of biosocial science 1998; 30(02): 261-275.
  19. Najmabadi H, Motazacker MM, Garshasbi M, Kahrizi K, Tzschach A, Chen W et al. Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci. Human genetics 2007; 121(1): 43-48.
  20. Haddad LA, Mingroni-Netto RC, Vianna-Morgante AM, Pena SD. A PCR-based test suitable for screening for fragile X syndrome among mentally retarded males. Human genetics 1996; 97(6): 808-812.
  21. Gazal S, Sahbatou M, Babron M-C, Génin E, Leutenegger A-L. FSuite: exploiting inbreeding in dense SNP chip and exome data. Bioinformatics 2014; 30(13): 1940-1941.
  22. Gazal S, Sahbatou M, Babron MC, Genin E, Leutenegger AL. FSuite: exploiting inbreeding in dense SNP chip and exome data. Bioinformatics 2014; 30(13): 1940-1941.
  23. Mir A, Sritharan K, Mittal K, Vasli N, Araujo C, Jamil T et al. Truncation of the E3 ubiquitin ligase component FBXO31 causes non-syndromic autosomal recessive intellectual disability in a Pakistani family. Human genetics 2014; 133(8): 975-984.
  24. Stenson PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS et al. Human gene mutation database (HGMD®): 2003 update. Human mutation 2003; 21(6): 577-581.
  25. Noor A, Windpassinger C, Patel M, Stachowiak B, Mikhailov A, Azam M et al. CC2D2A, encoding a coiled-coil and C2 domain protein, causes autosomal-recessive mental retardation with retinitis pigmentosa. The American Journal of Human Genetics 2008; 82(4): 1011-1018.
  26. Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, Otto EA et al. Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 2011; 145(4): 513-528.
  27. Khan MA, Rafiq MA, Noor A, Hussain S, Flores JV, Rupp V et al. Mutation in NSUN2, which encodes an RNA methyltransferase, causes autosomal-recessive intellectual disability. The American Journal of Human Genetics 2012; 90(5): 856-863.
  28. Johansen A, Rosti RO, Musaev D, Sticca E, Harripaul R, Zaki M et al. Mutations in MBOAT7, Encoding Lysophosphatidylinositol Acyltransferase I, Lead to Intellectual Disability Accompanied by Epilepsy and Autistic Features. The American Journal of Human Genetics 2016.
  29. Marangi G, Leuzzi V, Manti F, Lattante S, Orteschi D, Pecile V et al. TRAPPC9-related autosomal recessive intellectual disability: report of a new mutation and clinical phenotype. European Journal of Human Genetics 2013; 21(2): 229-232.
  30. Van Scherpenzeel M, Timal S, Rymen D, Hoischen A, Wuhrer M, Hipgrave-Ederveen A et al. Diagnostic serum glycosylation profile in patients with intellectual disability as a result of MAN1B1 deficiency. Brain 2014; 137(4): 1030-1038.
  31. Narasimhan VM, Hunt KA, Mason D, Baker CL, Karczewski KJ, Barnes MR et al. Health and population effects of rare gene knockouts in adult humans with related parents. Science 2016; 352(6284): 474-477.
  32. Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K, Willert RA, Achilly NP et al. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PloS one 2012; 7(1): e28936.
  33. Mochida GH, Mahajnah M, Hill AD, Basel-Vanagaite L, Gleason D, Hill RS et al. A truncating mutation of TRAPPC9 is associated with autosomal-recessive intellectual disability and postnatal microcephaly. The American Journal of Human Genetics 2009; 85(6): 897-902.
  34. Philippe O, Rio M, Carioux A, Plaza J-M, Guigue P, Molinari F et al. Combination of linkage mapping and microarray-expression analysis identifies NF-κB signaling defect as a cause of autosomal-recessive mental retardation. The American Journal of Human Genetics 2009; 85(6): 903-908.
  35. Jamra RA, Wohlfart S, Zweier M, Uebe S, Priebe L, Ekici A et al. Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity. European Journal of Human Genetics 2011; 19(11): 1161-1166.
  36. Kakar N, Goebel I, Daud S, Nürnberg G, Agha N, Ahmad A et al. A homozygous splice site mutation in TRAPPC9 causes intellectual disability and microcephaly. European journal of medical genetics 2012; 55(12): 727-731.
  37. van der Vaart B, Franker MA, Kuijpers M, Hua S, Bouchet BP, Jiang K et al. Microtubule plus-end tracking proteins SLAIN1/2 and ch-TOG promote axonal development. The Journal of Neuroscience 2012; 32(42): 14722-14728.
  38. Wright CF, Fitzgerald TW, Jones WD, Clayton S, McRae JF, Van Kogelenberg M et al. Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data. The Lancet 2015; 385(9975): 1305-1314.
  39. Franić S, Groen-Blokhuis MM, Dolan CV, Kattenberg MV, Pool R, Xiao X et al. Intelligence: shared genetic basis between Mendelian disorders and a polygenic trait. European Journal of Human Genetics 2015.
  40. Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacological reviews 2012; 64(2): 238-258.
  41. Chen WG, Chang Q, Lin Y, Meissner A, West AE, Griffith EC et al. Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2. Science 2003; 302(5646): 885-889.
  42. Dong E, Ruzicka W, Grayson D, Guidotti A. DNA-methyltransferase1 (DNMT1) binding to CpG rich GABAergic and BDNF promoters is increased in the brain of schizophrenia and bipolar disorder patients. Schizophrenia research 2015; 167(1): 35-41.
  43. Dong E, Gavin DP, Chen Y, Davis J. Upregulation of TET1 and downregulation of APOBEC3A and APOBEC3C in the parietal cortex of psychotic patients. Translational psychiatry 2012; 2(9): e159.
  44. Zhang R-R, Cui Q-Y, Murai K, Lim YC, Smith ZD, Jin S et al. Tet1 regulates adult hippocampal neurogenesis and cognition. Cell Stem Cell 2013; 13(2): 237-245.
  45. Li C, Lan Y, Schwartz-Orbach L, Korol E, Tahiliani M, Evans T et al. Overlapping Requirements for Tet2 and Tet3 in Normal Development and Hematopoietic Stem Cell Emergence. Cell reports 2015; 12(7): 1133-1143.
  46. Metsu S, Rooms L, Rainger J, Taylor MS, Bengani H, Wilson DI et al. FRA2A is a CGG repeat expansion associated with silencing of AFF3. PLoS Genet 2014; 10(4): e1004242.
  47. Wade EM, Daniel PB, Jenkins ZA, McInerney-Leo A, Leo P, Morgan T et al. Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia. The American Journal of Human Genetics 2016; 99(2): 392-406.
  48. Le Goff C, Rogers C, Le Goff W, Pinto G, Bonnet D, Chrabieh M et al. Heterozygous Mutations in MAP3K7, Encoding TGF-β-Activated Kinase 1, Cause Cardiospondylocarpofacial Syndrome. The American Journal of Human Genetics 2016; 99(2): 407-413.
  49. Hu H, Haas S, Chelly J, Van Esch H, Raynaud M, de Brouwer A et al. X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes. Molecular psychiatry 2016; 21(1): 133-148.
  50. Rual J-F, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N et al. Towards a proteome- scale map of the human protein-protein interaction network. Nature 2005; 437(7062): 1173- 1178.
  51. Rolland T, Taşan M, Charloteaux B, Pevzner SJ, Zhong Q, Sahni N et al. A proteome-scale map of the human interactome network. Cell 2014; 159(5): 1212-1226.
  52. Yu H, Tardivo L, Tam S, Weiner E, Gebreab F, Fan C et al. Next-generation sequencing to generate interactome datasets. Nature methods 2011; 8(6): 478-480.
  53. McCarthy SE, Gillis J, Kramer M, Lihm J, Yoon S, Berstein Y et al. De novo mutations in schizophrenia implicate chromatin remodeling and support a genetic overlap with autism and intellectual disability. Molecular psychiatry 2014; 19(6): 652.
  54. Mittal K, Rafiq MA, Rafiullah R, Harripaul R, Ali H, Ayaz M et al. Mutations in the genes for thyroglobulin and thyroid peroxidase cause thyroid dyshormonogenesis and autosomal- recessive intellectual disability. Journal of Human Genetics 2016.
  55. Pagnamenta AT, Bacchelli E, de Jonge MV, Mirza G, Scerri TS, Minopoli F et al. Characterization of a family with rare deletions in CNTNAP5 and DOCK4 suggests novel risk loci for autism and dyslexia. Biological psychiatry 2010; 68(4): 320-328.
  56. Kevelam SH, van Harssel JJ, van der Zwaag B, Smeets HJ, Paulussen AD, Lichtenbelt KD. A patient with a mild holoprosencephaly spectrum phenotype and heterotaxy and a 1.3 Mb deletion encompassing GLI2. American Journal of Medical Genetics Part A 2012; 158(1): 166-173.
  57. Barber JC, Maloney VK, Bewes B, Wakeling E. Deletions of 2q14 that include the homeobox engrailed 1 (EN1) transcription factor are compatible with a normal phenotype. European journal of human genetics 2006; 14(6): 739-743.
  58. Khan MA, Rafiq MA, Noor A, Ali N, Ali G, Vincent JB et al. A novel deletion mutation in the TUSC3 gene in a consanguineous Pakistani family with autosomal recessive nonsyndromic intellectual disability. BMC medical genetics 2011; 12(1): 56.
  59. Rafiq MA, Leblond CS, Saqib MA, Vincent AK, Ambalavanan A, Khan FS et al. Novel VPS13B Mutations in Three Large Pakistani Cohen Syndrome Families Suggests a Baloch Variant with Autistic-Like Features. BMC medical genetics 2015; 16(1): 41.
  60. Hall J, Owen MJ. Psychiatric classification-a developmental perspective. The British Journal of Psychiatry 2015; 207(4): 281-282.
  61. Purcell SM, Moran JL, Fromer M, Ruderfer D, Solovieff N, Roussos P et al. A polygenic burden of rare disruptive mutations in schizophrenia. Nature 2014; 506(7487): 185-190.
  62. Fromer M, Pocklington AJ, Kavanagh DH, Williams HJ, Dwyer S, Gormley P et al. De novo mutations in schizophrenia implicate synaptic networks. Nature 2014; 506(7487): 179-184.
  63. Nan X, Hou J, Maclean A, Nasir J, Lafuente MJ, Shu X et al. Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation. Proceedings of the National Academy of Sciences 2007; 104(8): 2709-2714.
  64. Colantuoni C, Lipska BK, Ye T, Hyde TM, Tao R, Leek JT et al. Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature 2011; 478(7370): 519-523.
  65. Huang J, Zhu T, Qu Y, Mu D. Prenatal, Perinatal and Neonatal Risk Factors for Intellectual Disability: A Systemic Review and Meta-Analysis. PloS one 2016; 11(4): e0153655.
  66. Singh T, Kurki MI, Curtis D, Purcell SM, Crooks L, McRae J et al. Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nature neuroscience 2016; 19: 571-7.
  67. Li J, Cai T, Jiang Y, Chen H, He X, Chen C et al. Genes with de novo mutations are shared by four neuropsychiatric disorders discovered from NPdenovo database. Molecular psychiatry 2015; 21: 298.
  68. Sun L, Dimitromanolakis A. PREST-plus identifies pedigree errors and cryptic relatedness in the GAW18 sample using genome-wide SNP data. BMC proceedings 2014; 8(Suppl 1): S23l.
  69. Philips AK, Pinelli M, de Bie CI, Mustonen A, Määttä T, Arts HH et al. Identification of C12orf4 as a gene for autosomal recessive intellectual disability. Clinical Genetics 2016; 91: 100-105.
  70. Alazami AM, Patel N, Shamseldin HE, Anazi S, Al-Dosari MS, Alzahrani F et al. Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. Cell reports 2015; 10(2): 148-161.
  71. Vasli N, Ahmed I, Mittal K, Ohadi M, Mikhailov A, Rafiq MA et al. Identification of a homozygous missense mutation in LRP2 and a hemizygous missense mutation in TSPYL2 in a family with mild intellectual disability. Psychiatric genetics 2016; 26(2): 66-73.
  72. Garshasbi M, Hadavi V, Habibi H, Kahrizi K, Kariminejad R, Behjati F et al. A defect in the TUSC3 gene is associated with autosomal recessive mental retardation. The American Journal of Human Genetics 2008; 82(5): 1158-1164.
  73. Celis K, Shuldiner S, Haverfield EV, Cappell J, Yang R, Gong D-W et al. Loss of function mutation in glutamic pyruvate transaminase 2 (GPT2) causes developmental encephalopathy. Journal of inherited metabolic disease 2015; 38(5): 941-948.
  74. Caldovic L, Morizono H, Panglao MG, Cheng SF, Packman S, Tuchman M. Null mutations in the N- acetylglutamate synthase gene associated with acute neonatal disease and hyperammonemia. Human genetics 2003; 112(4): 364-368.
  75. Kutsche K, Yntema H, Brandt A, Jantke I, Nothwang HG, Orth U et al. Mutations in ARHGEF6, encoding a guanine nucleotide exchange factor for Rho GTPases, in patients with X-linked mental retardation. Nature genetics 2000; 26(2): 247-250.
  76. Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nature genetics 1999; 23(2): 185-188 PK34 UBA7 Chr3:49848458C>A (8.01E-04/5.45E-03) NM_003335.2:c.1189G>T (p.Glu397*) 5 PJ9 TBC1D23 Chr3:100037953delA (0/0) NM_018309.4:c.1683delA (p.Glu562Argfs*3) 6 AN50 ZBTB11 Chr3:101371344A>C (0/0) NM_014415.3:c.2640T>G (p.His880Gln)

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Authors
Harripaul, R., Vasli, N., Mikhailov, A., Rafiq, M. A., Mittal, K., Windpassinger, C., Sheikh, T. I., Noor, A., Mahmood, H., Downey, S., Johnson, M., Vleuten, K., Bell, L., Ilyas, M., Khan, F. S., Khan, V, Moradi, M., Ayaz, M., Naeem, F., Heidari, A., Ahmed, I., Ghadami, S., Agha, Z., Zeinali, S., Qamar, R., Mozhdehipanah, H., John, P., Mir, A., Ansar, M., French, L., Ayub, M., & Vincent, J. B.
Affiliations
  • Centre for Addiction and Mental Health (CA)
  • Medical University of Graz (AT)
  • Mount Sinai Hospital (CA)
  • International Islamic University, Islamabad (PK)
  • Quaid-i-Azam University (PK)
  • Qazvin University of Medical Sciences (IR)
  • Queen's University (CA)
  • National University of Sciences and Technology (PK)
  • Pasteur Institute of Iran (IR)
  • COMSATS University Islamabad (PK)
Corresponding author
  • Ayub, M
  • Vincent, J B
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2017-04-11
Volume
23
Issue
4
Pages
973-984
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/mp.2017.60
OpenAlex
W2951249912
Cited by
175
References
7
Citations by year
2026: 9 · 2025: 11 · 2024: 19 · 2023: 18 · 2022: 21 · 2021: 26 · 2020: 25 · 2019: 13 · 2018: 24 · 2017: 8
FWCI
12.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
Funders
  • Radboud Universiteit
  • Tehran University of Medical Sciences and Health Services
  • Radboud Universitair Medisch Centrum
  • Peterborough K. M. Hunter Charitable Foundation
  • Canadian Institutes of Health Research (102758_1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
Keywords
autosomal recessive intellectual disability, consanguinity, homozygosity mapping, copy number variation, novel candidate genes, loss-of-function mutations, brain-derived neurotrophic factor, TET1, neuropsychiatric disorders, genetic heterogeneity
MeSH terms
Exome Sequencing, Loss of Function Mutation, Adult, Chromosome Mapping, Consanguinity, Family, Female, Genes, Recessive, Homozygote, Humans, Iran, Male, Intellectual Disability, Middle Aged, Mutation, Pakistan, Pedigree, Genetic Heterogeneity, Microarray Analysis, DNA Copy Number Variations

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