Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci
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Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR) has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects that account for more than a few percent of the cases.
KeywordsDown Syndrome Intelligence Quotient Consanguineous Family GJB2 Gene Homozygosity Mapping
We thank Jürg Ott for his advice concerning the significance levels of LOD scores in whole genome linkage studies, and Hannelore Markert for assisting us with the preparation of the manuscript. We are grateful to all patients, parents and other relatives for their active participation in this study, and to numerous genetic counselors and other health care professionals for their assistance. This study would not have been possible without support from the Deputy of Research, Iranian Ministry of Health and Medical Education (to HN) and a grant of the Max Planck Innovation Funds (to HHR).
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