RESUMO
Moebius syndrome is a rare disorder primarily characterized by congenital facial palsy, frequently accompanied by ocular abduction anomalies, and occasionally associated with orofacial, limb and musculoskeletal malformations. Abnormal development of cranial nerves V through XII underlines the disease pathogenesis. Although some investigations suggested that a causative gene may lie on 13q12.2-q13, there have been no molecular studies targeting possible microdeletions in this region to date. In the present study, we performed microdeletion analyses on 13q12.11-q13 in nine patients, and sequenced three candidate genes in nineteen patients for functional relevance and further resolution of our screening. We ruled out microdeletions on the critical region as a common cause of Moebius syndrome and excluded FGF9, GSH1 and CDX2 genes.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 13 , Paralisia Facial/genética , Testes Genéticos , Síndrome de Möbius/genética , Alelos , Fator de Transcrição CDX2 , DNA/genética , DNA/isolamento & purificação , Primers do DNA/química , Bases de Dados Genéticas , Fator 9 de Crescimento de Fibroblastos/genética , Marcadores Genéticos , Genótipo , Glutationa Sintase/genética , Haplótipos , Proteínas de Homeodomínio/genética , Homozigoto , Humanos , Repetições de Microssatélites , Técnicas de Amplificação de Ácido Nucleico , Mapeamento Físico do Cromossomo , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
Möbius syndrome is a rare disorder primarily characterized by congenital facial palsy, frequently accompanied by ocular abduction anomalies and occasionally associated with orofacial, limb and musculoskeletal malformations. Abnormal development of cranial nerves V through XII underlines the disease pathogenesis. Although a genetic etiology for Möbius syndrome was proposed, molecular genetic studies to identify the causative gene(s) are scarce. In this study, we selected two candidate genes. One is BASP1 residing in a human chromosome 5p15.1-p15.2, syntenic to mouse chromosome 15qA2-qB2, to which a mouse model with facial nerve anomalies was mapped. The other is transcribed processed pseudogene TPPsig-BASP1, which is located on chromosome 13q flanking the putative locus for Möbius syndrome and might be involved in the regulation of the transcripts encoded by BASP1. Mutation analyses in nineteen patients excluded these genes as being candidates for Möbius syndrome.
