Zhijie Niu1, Yong Feng2, Zhengmao Hu3, Jiada Li3, Jie Sun4, Hongsheng Chen5, Chufeng He5, Xueping Wang5, Lu Jiang5, Yalan Liu5, Xinzhang Cai5, Lili Wang5, Yuxiang Cai5, Xuezhong Liu1, Lingyun Mei6. 1. Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, 410008, China; Department of Otolaryngology (D-48), University of Miami Miller School of Medicine, 1666 NW 12th Avenue, Miami, FL 33136, USA. 2. Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, 410008, China; State Key Laboratory of Medical Genetics, Central South University, Changsha, 410078, China. 3. State Key Laboratory of Medical Genetics, Central South University, Changsha, 410078, China. 4. Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, 410008, China; Department of Otorhinolaryngology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, China. 5. Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, 410008, China. 6. Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, 410008, China; Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, 410008, China. Electronic address: entmly@163.com.
Abstract
OBJECTIVE: Autosomal dominant non-syndromic low-frequency sensorineural hearing loss (LFSNHL) DFNA6/14/38 is an uncommon type of hearing loss that classically affects low frequencies of 2000 Hz and below, demonstrating an ascending configuration. The current study aimed to investigate the cause of LFSNHL in a five-generation Chinese family. METHODS: The phenotype of the Chinese family was characterized using audiologic testing and pedigree analysis. The combined approach of array screening and whole-exome sequencing was used to identify the disease-causing gene in this family. RESULTS: This pedigree, in which the affected subjects presented isolated low-frequency sensorineural hearing impairment with childhood onset, was associated with autosomal dominant inheritance of the c.2591A > G mutation in exon 8 of the Wolframin syndrome 1 (WFS1) gene which was not present in 286 unrelated controls with matched ancestry and is highly conserved across species. In addition, several mutations affecting the Glu864 residue have been previously identified in different populations, suggesting that this site is likely to be a mutational hot spot. CONCLUSIONS: We identified a novel substitution, Glu864Gly, of WFS1 as the causative variant for this pedigree. Our data extend the mutation spectrum of the WFS1 gene in Chinese individuals and may contribute to establishing a better genotype-phenotype correlation for LFSNHL.
OBJECTIVE: Autosomal dominant non-syndromic low-frequency sensorineural hearing loss (LFSNHL) DFNA6/14/38 is an uncommon type of hearing loss that classically affects low frequencies of 2000 Hz and below, demonstrating an ascending configuration. The current study aimed to investigate the cause of LFSNHL in a five-generation Chinese family. METHODS: The phenotype of the Chinese family was characterized using audiologic testing and pedigree analysis. The combined approach of array screening and whole-exome sequencing was used to identify the disease-causing gene in this family. RESULTS: This pedigree, in which the affected subjects presented isolated low-frequency sensorineural hearing impairment with childhood onset, was associated with autosomal dominant inheritance of the c.2591A > G mutation in exon 8 of the Wolframin syndrome 1 (WFS1) gene which was not present in 286 unrelated controls with matched ancestry and is highly conserved across species. In addition, several mutations affecting the Glu864 residue have been previously identified in different populations, suggesting that this site is likely to be a mutational hot spot. CONCLUSIONS: We identified a novel substitution, Glu864Gly, of WFS1 as the causative variant for this pedigree. Our data extend the mutation spectrum of the WFS1 gene in Chinese individuals and may contribute to establishing a better genotype-phenotype correlation for LFSNHL.
Authors: Ryan K Thorpe; W Daniel Walls; Rae Corrigan; Amanda Schaefer; Kai Wang; Patrick Huygen; Thomas L Casavant; Richard J H Smith Journal: Hum Genet Date: 2022-01-17 Impact factor: 5.881
Authors: Luciana Rigoli; Valerio Caruso; Giuseppina Salzano; Fortunato Lombardo Journal: Int J Environ Res Public Health Date: 2022-03-09 Impact factor: 3.390
Authors: Raíssa de Oliveira Aquino Schüffner; Karla Lima Nascimento; Fábio André Dias; Pedro Henrique Teodoro da Silva; Wrgelles Godinho Bordone Pires; Nilson Moreira Cipriano; Luciana Lara Dos Santos Journal: Braz J Otorhinolaryngol Date: 2019-02-20