Reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment

Xiong, Wenping; Wang, Dayong; Gao, Yuan; Gao, Ya; Wang, HongYang; Guan, Jing; Lan, Lan; Yan, Junhao; Zong, Lei; Yuan, Yuan; Dong, Wei; Huang, Sexin; Wu, Keliang; Wang, Yaoshen; Wang, ZhiLi; Peng, Hongmei; Lu, Yanping; Xie, Linyi; Zhao, Cui; Wang, Li; Zhang, Qiu-Jing; Gao, Yun; Li, Na; Yang, Ju Dong; Yin, Zifang; Han, Bing; Wang, Wei; Chen, Zi‐Jiang

doi:10.1007/s11427-015-4936-y

“…Newborn concurrent hearing and genetic screening16 are recommended for all of the offspring of gene mutation carriers to provide early diagnosis and intervention. Prenatal testing for pregnancies at increased risk is also possible; the mutation carriers can also choose preconception testing and diagnosis of their own accord15.…”

Section: Discussionmentioning

confidence: 99%

A novel dominant GJB2 (DFNA3) mutation in a Chinese family

Wang

¹

,

Wu

²

,

Yu

³

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

To decipher the phenotype and genotype of a Chinese family with autosomal dominant non-syndromic hearing loss (ADNSHL) and a novel dominant missense mutation in the GJB2 gene (DFNA3), mutation screening of GJB2 was performed on the propositus from a five-generation ADNSHL family through polymerase chain reaction amplification and Sanger sequencing. The candidate variation and the co-segregation of the phenotype were verified in all ascertained family members. Targeted genes capture and next-generation sequencing (NGS) were performed to explore additional genetic variations. We identified the novel GJB2 mutation c.524C > A (p.P175H), which segregated with high frequency and was involved in progressive sensorineural hearing loss. One subject with an additional c.235delC mutation showed a more severe phenotype than did the other members with single GJB2 dominant variations. Four patients diagnosed with noise-induced hearing loss did not carry this mutation. No other pathogenic variations or modifier genes were identified by NGS. In conclusion, a novel missense mutation in GJB2 (DFNA3), affecting the second extracellular domain of the protein, was identified in a family with ADNSHL.

show abstract

“…Establishing a genetic diagnosis can alleviate parental guilt and anxiety, lay a foundation for future genetic counseling and provide prognostic information 15 . The offspring of an affected individual with the GJB2 mutation in Family 304 had a 50% chance of inheriting the altered gene, except for IV:22 and the four noise-induced hearing loss members.…”

Section: Discussionmentioning

confidence: 99%

“…Newborn concurrent hearing and genetic screening 16 are recommended for all of the offspring of gene mutation carriers to provide early diagnosis and intervention. Prenatal testing for pregnancies at increased risk is also possible; the mutation carriers can also choose preconception testing and diagnosis of their own accord 15 . In summary, we identified a novel DFNA3 mutation in a Chinese family with ADNSHL and performed phenotype-genotype correlation analysis.…”

Section: Discussionmentioning

confidence: 99%

A novel dominant GJB2 (DFNA3) mutation in a Chinese family

Wang

¹

2017

The Journal of the Acoustical Society of America

Self Cite

View full text Add to dashboard Cite

To decipher the phenotype and genotype of a Chinese family with autosomal dominant non-syndromic hearing loss (ADNSHL) and a novel dominant missense mutation in the GJB2 gene (DFNA3), mutation screening of GJB2 was performed on the propositus from a five-generation ADNSHL family through polymerase chain reaction amplification and Sanger sequencing. The candidate variation and the cosegregation of the phenotype were verified in all ascertained family members. Targeted genes capture and next-generation sequencing (NGS) were performed to explore additional genetic variations. We identified the novel GJB2 mutation c.524C > A (p.P175H), which segregated with high frequency and was involved in progressive sensorineural hearing loss. One subject with an additional c.235delC mutation showed a more severe phenotype than did the other members with single GJB2 dominant variations. Four patients diagnosed with noise-induced hearing loss did not carry this mutation. No other pathogenic variations or modifier genes were identified by NGS. In conclusion, a novel missense mutation in GJB2 (DFNA3), affecting the second extracellular domain of the protein, was identified in a family with ADNSHL.Mutations in the gene GJB2, which encodes the gap junction protein connexin 26, play a key role in hereditary hearing loss and represent the most common cause of non-syndromic hearing loss 1 . Variations in GJB2 may cause either autosomal dominant or recessive non-syndromic hearing loss (NSHL) as well as syndromic hearing loss (SHL). The inheritance pattern is ultimately determined by how the variation affects the expression and function of the connexin 26 protein. More than two hundred mutations in GJB2 (DFNB1, MIM220290) have been found to be related to autosomal recessive non-syndromic hearing loss 2 , whereas only nineteen GJB2 mutations have been associated with hereditary autosomal dominant non-syndromic deafness (DFNA3, MIM601544). Previous studies of dominant GJB2 mutations are rare and have been limited to cases or simplex families. In this study, via traditional PCR and Sanger sequencing, a novel GJB2 heterozygous mutation was identified in a Chinese family with autosomal dominant non-syndromic hearing loss (ADNSHL). Results Clinical description. From Family 304, a total of 32 family members, including 16 clinically affected and 16unaffected individuals, were included in this study (Fig. 1). Among the 16 affected cases, 4 subjects had explicit noise exposure history. In this family, the 12 affected members without noise exposure history showed symmetrical and bilateral non-syndromic sensorineural hearing loss, but no clear onset age was described (although the ages of identification were generally within childhood). The propositus (IV:2) was a 26-year-old male with bilateral progressive hearing loss when he first visited our outpatient clinic in 2004. The hearing impairment initially presented at high frequencies. He showed moderate or mild hearing loss at 0.5 kHz and 1 kHz and severe or profound hearing loss at 2 kHz, 4 kHz and ...

show abstract

“…There are important factors to be considered when choosing a genetic test, such as patient's history and phenotype [78] . The identification of a genetic hearing disorder is important as it may improve prognostic accuracy and may allow a correct genetic counseling for the affected patient and relatives at risk [79,80] . Also, the genetician may provide information to parents among inheritance modalities and the pre-natal diagnosis if available [81,82] .…”

Section: Diagnostic Work-up Of Moderate-severe Hearing Loss In Childrenmentioning

confidence: 99%