X-linked intellectual disability related genes disrupted by balanced X-autosome translocations

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Moyses-Oliveira, Mariana ^[1] ; Guilherme, Roberta Santos ^{[1, 2]} ; Meloni, Vera Ayres ^[1] ; Di Battista, Adriana ^[1] ; de Mello, Claudia Berlim ^[3] ; Bragagnolo, Silvia ^[1] ; Moretti-Ferreira, Danilo ^[4] ; Kosyakova, Nadezda ^[2] ; Liehr, Thomas ^[2] ; Carvalheira, Gianna Maria ^[1] ; Melaragno, Maria Isabel ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Morphol & Genet, Div Genet, BR-04023900 Sao Paulo, SP - Brazil

^[2] Univ Jena, Jena Univ Hosp, Inst Human Genet, Jena - Germany

^[3] Univ Fed Sao Paulo, Dept Psychobiol, BR-04023900 Sao Paulo, SP - Brazil

^[4] Univ Estadual Sao Paulo, Inst Biocincias Botucatu, Dept Genet, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS; v. 168, n. 8, p. 669-677, DEC 2015.
• Citações Web of Science: 15

Resumo

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 (TSPAN7MRX58, KIAA2022MRX98, and IL1RAPL1MRX21/34) 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. (C) 2015 Wiley Periodicals, Inc. (AU)

• Processo FAPESP: 11/51690-1 - Translocações X-autossomo: investigação da reorganização da cromatina e do efeito na função ovariana
• Beneficiário: Maria Isabel de Souza Aranha Melaragno
• Linha de fomento: Auxílio à Pesquisa - Regular