Short Original Article
Identification and genetic analysis of new mutations in EYA1 gene of BOS syndrome
Ma Jing, Huang Rui, Ma Xiuli, Li Xia, Zhang Tiesong, Ruan Biao
Published 2021-09-07
Cite as Chin J Otorhinolaryngol Head Neck Surg, 2021, 56(9): 966-971. DOI: 10.3760/cma.j.cn115330-20210126-00040
Abstract
ObjectiveTo analyze the clinical manifestations of a patient with branchiootic syndrome(BOS) and her families and to carry out genetic testing in order to specify the biological pathogenesis.
MethodsClinical data of the patient and her families were collected. Genomic DNA in the peripheral blood of the proband and her family members was extracted. All exons of 406 deafness-related susceptible genes as well as their flanking regions were sequenced by high-throughput sequencing, and the mutation sites of the proband and her parents were validated by Sanger sequencing.
ResultsThere were nine members in three generations, of whom four presented with hearing loss, preauricular fistula and branchial fistula which met the diagnostic criteria of BOS. Proband and her mother presented with auricle malformation and inner ear malformation. And no one had abnormalities in the kidneys of all the patients. Pedigree analysis revealed that the mode of inheritance in the family was consistent with the autosomal dominant pattern. Mutational analysis showed that all the affected patients detected a heterozygous frameshift variation c.1255delT in the EYA1 gene, which had not been reported. Genotype and phenotype were co-isolated in this family. Such a frameshift variation produced a premature termination codon, thereby causing premature termination of translation (p.C419VFS*12). ACMG identified that the mutation was pathogenic. This mutation was novel and not detected in controls. A heterozygous missense variation mutation c.403G>A(p.G135S) inEYA1 gene was also detected in three members of this family. ACMG identified that the mutation clinical significance was uncertain. However, two of whom were normal, which seemed the disease was not caused by this mutation in this family.
ConclusionsA novel frameshift mutation in EYA1(c.1255delT) is the main molecular etiology of BOS in the Chinese family. This study expands the mutational spectrum of EYA1 gene. The clinical manifestations are heterogeneous among patients in this family. The diagnosis of BOS should combine gene tests with clinical phenotypes analysis.
Key words:
Branchiootic syndrome; EYA1; Hereditary hearing loss; DNA mutational analysis
Contributor Information
Ma Jing
Department of Otorhinolaryngology Head and Neck Surgery, Kunming Children′s Hospital, Kunming Key Laboratory for Prevention and Control of Congenital Birth Defects of Children, Yunnan Key Laboratory of Children′s Major Disease Research, Kunming 650228, China
Huang Rui
Department of Otorhinolaryngology Head and Neck Surgery, Kunming Children′s Hospital, Kunming Key Laboratory for Prevention and Control of Congenital Birth Defects of Children, Yunnan Key Laboratory of Children′s Major Disease Research, Kunming 650228, China
Ma Xiuli
Department of Otorhinolaryngology Head and Neck Surgery, Kunming Children′s Hospital, Kunming Key Laboratory for Prevention and Control of Congenital Birth Defects of Children, Yunnan Key Laboratory of Children′s Major Disease Research, Kunming 650228, China
Li Xia
Department of Otorhinolaryngology Head and Neck Surgery, Kunming Children′s Hospital, Kunming Key Laboratory for Prevention and Control of Congenital Birth Defects of Children, Yunnan Key Laboratory of Children′s Major Disease Research, Kunming 650228, China
Zhang Tiesong
Department of Otorhinolaryngology Head and Neck Surgery, Kunming Children′s Hospital, Kunming Key Laboratory for Prevention and Control of Congenital Birth Defects of Children, Yunnan Key Laboratory of Children′s Major Disease Research, Kunming 650228, China
Ruan Biao
Department of Otorhinolaryngology, the First Hospital of Kunming Medical University, Kunming 650032, China
