Abstract:
BACKGROUND:Intellectual disability (ID) is a highly heterogeneous condition affecting 2% of the population worldwide. In a field study conducted in a highly inbred area of Northeastern Brazil, we investigated a consanguineous family in which seven adults presented syndromic ID. METHODS:Genome-Wide Human SNP Array 6.0 (Affymetrix) microarray was used to determine regions of homozygosity-by-descent and whole exome sequencing (WES) was performed in one affected individual using Extended Nextera Rapid-Capture Exome and Illumina HiSeq2500. RESULTS:We found two regions with an logarithm of the odds (LOD) score of 3.234: a region spanning 4.0 Mb in 19q13.32-q13.33 and a pericentromeric 20 Mb area in chromosome 2 (2p12-q11.2). WES disclosed in the critical region of chromosome 19 a homozygous variant (c.418C>T, p.Arg140Trp) in Mediator complex subunit 25 (MED25), predicted as deleterious by PolyPhen-2, Provean, Mutation Taster and Sorting Intolerant From Tolerant (SIFT). MED25 is a component of the Mediator complex, involved in regulation of transcription of nearly all RNA polymerase II-dependent genes. Deleterious mutations in MED12, MED17 and MED23 have already been associated with ID. CONCLUSIONS:These findings demonstrate that the combination of field investigation of families in highly inbred regions with modern technologies is an effective way for identifying new genes associated with ID.
journal_name
J Med Genetjournal_title
Journal of medical geneticsauthors
Figueiredo T,Melo US,Pessoa AL,Nobrega PR,Kitajima JP,Correa I,Zatz M,Kok F,Santos Sdoi
10.1136/jmedgenet-2014-102793subject
Has Abstractpub_date
2015-02-01 00:00:00pages
123-7issue
2eissn
0022-2593issn
1468-6244pii
jmedgenet-2014-102793journal_volume
52pub_type
杂志文章abstract::We report here a father and daughter with digital abnormalities, nasolacrimal duct obstruction, and variable alopecia. The father had a cleft lip and palate and the daughter had choanal atresia. We propose they both have the EEC syndrome and show the variable expressivity of this disorder. Choanal atresia has not been...
journal_title:Journal of medical genetics
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journal_title:Journal of medical genetics
pub_type: 杂志文章
doi:
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journal_title:Journal of medical genetics
pub_type: 杂志文章,评审
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更新日期:2016-07-01 00:00:00
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更新日期:1980-08-01 00:00:00