Investigation of genetic factors underlying typical orofacial clefts: mutational screening and copy number variation

Autor(es)

Simioni, Milena ^[1] ; Araujo, Tania Kawasaki ^[1] ; Monlleo, Isabella Lopes ^{[2, 3]} ; Maurer-Morelli, Claudia Vianna ^[1] ; Gil-da-Silva-Lopes, Vera Lucia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, UNICAMP, Fac Med Sci, Dept Med Genet, BR-13083887 Campinas, SP - Brazil

^[2] Univ Fed Alagoas, Univ Hosp, Fac Med, Clin Genet Serv, Maceio, Alagoas - Brazil

^[3] Univ Fed Alagoas, Genet Sect, Maceio, Alagoas - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF HUMAN GENETICS; v. 60, n. 1, p. 17-25, JAN 2015.
• Citações Web of Science: 13

Resumo

Typical orofacial clefts (OFCs) comprise cleft lip, cleft palate and cleft lip and palate. The complex etiology has been postulated to involve chromosome rearrangements, gene mutations and environmental factors. A group of genes including IRF6, FOXE1, GLI2, MSX2, SKI, SATB2, MSX1 and FGF has been implicated in the etiology of OFCs. Recently, the role of the copy number variations (CNVs) has been studied in genetic defects and diseases. CNVs act by modifying gene expression, disrupting gene sequence or altering gene dosage. The aims of this study were to screen the above-mentioned genes and to investigate CNVs in patients with OFCs. The sample was composed of 23 unrelated individuals who were grouped according to phenotype (associated with other anomalies or isolated) and familial recurrence. New sequence variants in GLI2, MSX1 and FGF8 were detected in patients, but not in their parents, as well as in 200 control chromosomes, indicating that these were rare variants. CNV screening identified new genes that can influence OFC pathogenesis, particularly highlighting TCEB3 and KIF7, that could be further analyzed. The findings of the present study suggest that the mechanism underlying CNV associated with sequence variants may play a role in the etiology of OFC. (AU)

• Processo FAPESP: 08/10596-0 - Uso da técnica de SNP array para detecção de variações no número de cópias do DNA (copy number variation, CNV) em defeitos congênitos de herança complexa: as fendas orais como modelo
• Beneficiário: Vera Lúcia Gil da Silva Lopes
• Modalidade de apoio: Auxílio à Pesquisa - Regular