Homozygous missense mutation in MED25 segregates with syndromic intellectual disability in a large consanguineous family
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Citações na Scopus
22
Tipo de produção
article
Data de publicação
2015
Título da Revista
ISSN da Revista
Título do Volume
Editora
BMJ PUBLISHING GROUP
Autores
FIGUEIREDO, Thalita
MELO, Uira Souto
PESSOA, Andre Luiz Santos
KITAJIMA, Joao Paulo
CORREA, Igor
ZATZ, Mayana
SANTOS, Silvana
Citação
JOURNAL OF MEDICAL GENETICS, v.52, n.2, p.123-127, 2015
Resumo
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.
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