RESUMO
Laryngeal structural anomalies were described in 13 cases of Richieri-Costa Pereira syndrome, and four previously reported cases were reviewed. The 17 individuals examined had the typical laryngeal anomalies and vocal disorders previously described. The new findings are the laryngeal microweb observed in three cases and arytenoid anteriorization movement observed in 14 cases.
Assuntos
Pé Torto Equinovaro/patologia , Deformidades Congênitas da Mão/patologia , Laringe/anormalidades , Síndrome de Pierre Robin/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Adulto JovemRESUMO
Here we describe a novel missense variant in the KCNQ4 gene and a private duplication at 7q31.1 partially involving two genes (IMMP2L and DOCK4). Both mutations segregated with nonsyndromic hearing loss in a family with three affected individuals. Initially, we identified the duplication in a screening of 132 unrelated cases of hearing loss with a multiplex ligation-dependent probe amplification panel of genes that are candidates to have a role in hearing, including IMMP2L. Mapping of the duplication by array-CGH revealed that the duplication also encompassed the 3'-end of DOCK4. Subsequently, whole-exome sequencing identified the breakpoint of the rearrangement, thereby confirming the existence of a fusion IMMP2L-DOCK4 gene. Transcription products of the fusion gene were identified, indicating that they escaped nonsense-mediated messenger RNA decay. A missense substitution (c.701A>T) in KCNQ4 (a gene at the DFNA2A locus) was also identified by whole-exome sequencing. Because the substitution is predicted to be probably damaging and KCNQ4 has been implicated in hearing loss, this mutation might explain the deafness in the affected individuals, although a hypothetical effect of the product of the fusion gene on hearing cannot be completely ruled out.
RESUMO
Samples from 30 deaf probands exhibiting features suggestive of syndromic mitochondrial deafness or from families with maternal transmission of deafness were selected for investigation of mutations in the mitochondrial genes MT-RNR1 and MT-TS1. Patients with mutation m.1555A>G had been previously excluded from this sample. In the MT-RNR1 gene, five probands presented the m.827A>G sequence variant, of uncertain pathogenicity. This change was also detected in 66 subjects of an unaffected control sample of 306 Brazilian individuals from various ethnic backgrounds. Given its high frequency, we consider it unlikely to have a pathogenic role on hereditary deafness. As to the MT-TS1 gene, one proband presented the previously known pathogenic m.7472insC mutation and three probands presented a novel variant, m.7462C>T, which was absent from the same control sample of 306 individuals. Because of its absence in control samples and association with a family history of hearing impairment, we suggest it might be a novel pathogenic mutation.
Assuntos
DNA Mitocondrial/genética , Surdez/genética , Perda Auditiva Neurossensorial/genética , Mutação Puntual , RNA Ribossômico/genética , RNA de Transferência de Serina/genética , Brasil/epidemiologia , Surdez/etnologia , Etnicidade/genética , Feminino , Frequência do Gene , Genes Mitocondriais , Haplótipos/genética , Perda Auditiva Neurossensorial/etnologia , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , RNA Ribossômico/fisiologia , RNA de Transferência de Serina/fisiologiaRESUMO
We describe laryngeal malformations and voice disorders in two new patients with the autosomal recessive Richieri-Costa and Pereira form of acrofacial dysostosis. This report confirms the data on the first five patients we had already presented in 1996.