RT Journal Article SR Electronic T1 Homozygous missense mutation in MED25 segregates with syndromic intellectual disability in a large consanguineous family JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 123 OP 127 DO 10.1136/jmedgenet-2014-102793 VO 52 IS 2 A1 Thalita Figueiredo A1 Uirá Souto Melo A1 André Luiz Santos Pessoa A1 Paulo Ribeiro Nobrega A1 João Paulo Kitajima A1 Igor Correa A1 Mayana Zatz A1 Fernando Kok A1 Silvana Santos YR 2015 UL http://jmg.bmj.com/content/52/2/123.abstract AB 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.