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. 2011 Nov;19(11):1161-6.
doi: 10.1038/ejhg.2011.98. Epub 2011 Jun 1.

Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity

R Abou Jamra  1 , Sigrun Wohlfart, Markus Zweier, Steffen Uebe, Lutz Priebe, Arif Ekici, Susanne Giesebrecht, Ahmad Abboud, Mohammed Ayman Al Khateeb, Mahmoud Fakher, Saber Hamdan, Amina Ismael, Safia Muhammad, Markus M Nöthen, Johannes Schumacher, André Reis
Affiliations

Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity

R Abou Jamra et al. Eur J Hum Genet. 2011 Nov.

Abstract

Non-specific intellectual disability of autosomal recessive inheritance (NS-ARID) represents an important fraction of severe cognitive dysfunction disorders. To date, only 10 genes have been identified, and further 24 linked-ARID loci have been reported, as well as others with suggestive linkage. To discover novel genes causing NS-ARID, we undertook genome-wide homozygosity mapping in 64 consanguineous multiplex families of Syrian descent. A total of 11 families revealed unique, significantly linked loci at 4q26-4q28 (MRT17), 6q12-q15 (MRT18), 18p11 (MRT19), 16p12-q12 (MRT20), 11p15 (MRT21), 11p13-q14 (MRT23), 6p12 (MRT24), 12q13-q15 (MRT25), 14q11-q12 (MRT26), 15q23-q26 (MRT27), and 6q26-q27 (MRT28), respectively. Loci ranged between 1.2 and 45.6 Mb in length. One family showed linkage to chromosome 8q24.3, and we identified a mutation in TRAPPC9. Our study further highlights the extreme heterogeneity of NS-ARID, and suggests that no major disease gene is to be expected, at least in this study group. Systematic analysis of large numbers of affected families, as presented here, will help discovering the genetic causes of ID.

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Figures

Figure 1
Figure 1
Overview of NS-ARID loci reported to date, , , (blue bars), and novel loci reported here (red bars). Positions of known NS-ARID genes are marked with an arrow next to the gene symbol. Diagram was drawn with help of the GenomeGraph tool of the UCSC genome browser.
Figure 2
Figure 2
Overview of the 12 families, which showed one linkage locus. The families were simplified as possible, and important information such as healthy brothers of mothers or grandmothers are shown. Asterisks (*) indicate genotyped DNAs.
See this image and copyright information in PMC

References

    1. Ropers HH. Genetics of early onset cognitive impairment. Annu Rev Genomics Hum Genet. 2010;11:161–187. - PubMed
    1. Rauch A, Hoyer J, Guth S, et al. Diagnostic yield of various genetic approaches in patients with unexplained developmental delay or mental retardation. Am J Med Genet A. 2006;140:2063–2074. - PubMed
    1. Ropers HH, Hamel BC. X-linked mental retardation. Nat Rev Genet. 2005;6:46–57. - PubMed
    1. Bartley JA, Hall BD. Mental retardation and multiple congenital anomalies of unknown etiology: frequency of occurrence in similarly affected sibs of the proband. Birth Defects Orig Artic Ser. 1978;14:127–137. - PubMed
    1. Priest JH, Thuline HC, Laveck GD, Jarvis DB. An approach to genetic factors in mental retardation. Studies of families containing at least two siblings admitted to a state institution for the retarded. Am J Ment Defic. 1961;66:42–50. - PubMed

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