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X‐linked intellectual disability related genes disrupted by balanced X‐autosome translocations
Author(s) -
MoysésOliveira Mariana,
Guilherme Roberta Santos,
Meloni Vera Ayres,
Di Battista Adriana,
de Mello Claudia Berlim,
Bragagnolo Silvia,
MorettiFerreira Danilo,
Kosyakova Nadezda,
Liehr Thomas,
Carvalheira Gianna Maria,
Melaragno Maria Isabel
Publication year - 2015
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32355
Subject(s) - intellectual disability , chromosomal translocation , breakpoint , gene , genetics , biology , autosome , phenotype , x chromosome , gene expression , chromosome
Detailed molecular characterization of chromosomal rearrangements involving X‐chromosome has been a key strategy in identifying X‐linked intellectual disability‐causing genes. We fine‐mapped the breakpoints in four women with balanced X‐autosome translocations and variable phenotypes, in order to investigate the corresponding genetic contribution to intellectual disability. We addressed the impact of the gene interruptions in transcription and discussed the consequences of their functional impairment in neurodevelopment. Three patients presented with cognitive impairment, reinforcing the association between the disrupted genes ( TSPAN7 —MRX58, KIAA2022 —MRX98, and IL1RAPL1 —MRX21/34) and intellectual disability. While gene expression analysis showed absence of TSPAN7 and KIAA2022 expression in the patients, the unexpected expression of IL1RAPL1 suggested a fusion transcript ZNF611‐IL1RAPL1 under the control of the ZNF611 promoter, gene disrupted at the autosomal breakpoint. The X‐chromosomal breakpoint definition in the fourth patient, a woman with normal intellectual abilities, revealed disruption of the ZDHHC15 gene (MRX91). The expression assays did not detect ZDHHC15 gene expression in the patient, thus questioning its involvement in intellectual disability. Revealing the disruption of an X‐linked intellectual disability‐related gene in patients with balanced X‐autosome translocation is a useful tool for a better characterization of critical genes in neurodevelopment. © 2015 Wiley Periodicals, Inc.