GJB2 c.235delC variant associated with autosomal recessive nonsyndromic hearing loss and auditory neuropathy spectrum disorder

Hong, Xia; Huang, Xiangjun; Xu, Hongbo; Zhou, Yongan; Gong, Ling; Yang, Zhijian; Lv, Jingyan; Deng, Hao

doi:10.1590/1678-4685-gmb-2017-0318

Cited by 9 publications

(8 citation statements)

References 19 publications

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“…In 24 sporadic cases, the genetic testing indicated that 13 case had disease-causing mutations in AR IRD gene, 5 cases in AD IRD genes, 6 cases in XL IRD genes, thereby, their inheritance mode were rede ned. Importantly, the proband of Family P34 had deafness and CVD, HEDEP indicated that he had a homozygous deletion variant (c.235delC; p. Leu79Cysfs*3) in GJB2 gene, which has been reported to cause AR deafness, (Lin et al 2022;Xia et al 2019) while no CNV in GJB2 gene by qPCR was detected. The family denied consanguineous marriage, and his elder sister did not have this mutation; we wonder whether the mutation occurred only in the proband but was inherited from his parents.…”

Section: The Results Of the Cnv Analysismentioning

confidence: 99%

Screening Copy Number Variations in 35 unsolved Inherited Retinal Disease Families

Liu,

Dai,

et al. 2023

Preprint

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The purpose of this study was to screen Copy Number Variations (CNVs) in 35 unsolved Inherited Retinal Dystrophy (IRD) families. Initially, Next generation sequencing, including a specific Hereditary Eye Disease Enrichment Panel or Whole exome sequencing, was employed to screen (likely) pathogenic Single-nucleotide Variants (SNVs) and small Insertions and Deletions (indels) for these cases. All available SNVs and indels were further validated and co-segregation analyses were performed in available family members by Sanger sequencing. If not, after excluding deep intronic variants, Multiplex ligation-dependent probe amplification (MLPA), quantitative fluorescence PCR (QF-PCR) and Sanger sequencing were employed to screen CNVs. We determined that 18 families who had heterozygous SNVs/indels or whose parents were not consanguineous but had homozygous SNVs/indels in autosomal recessive IRDs genes had CNVs in another allele of these genes, 11 families had disease-causing hemizygous CNVs in X-linked IRD genes, six families had (likely) pathogenic heterozygous CNVs in PRPF31 gene. Of 35 families, 33 different CNVs in 16 IRD-associated genes were detected, with PRPF31, EYS and USH2A the most common disease-causing gene in CNVs. Twenty-six and seven of them were deletion and duplication CNVs, respectively. Among them, 14 CNVs were first reported in this study. Our research indicated that CNVs contribute a lot to IRDs, and screening of CNVs substantially increases the diagnostic rate of IRD. Our results indicate that MLPA and QF-PCR are ideal methods to validate CNVs, and the novel CNVs reported herein expand the mutational spectrums of IRD.

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Section: The Results Of the Cnv Analysismentioning

confidence: 99%

Screening Copy Number Variations in 35 unsolved Inherited Retinal Disease Families

Liu,

Dai,

et al. 2023

Preprint

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“…HaplotypeCaller of GATK was applied to call a raw variant set including single nucleotide polymorphisms (SNPs) and indels. Hard-filtering methods with proper parameters were used to filter SNPs and indels (Xia et al, 2018;Xia et al, 2019). The resulting highconfident SNPs and indels were further annotated by a SnpEff tool (https://pcingola.github.io/SnpEff/).…”

Section: Variant Analysismentioning

confidence: 99%

Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder

Yuan

Xiao

et al. 2023

Front. Mol. Biosci.

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Most internal organs in humans and other vertebrates exhibit striking left-right asymmetry in position and structure. Variation of normal organ positioning results in left-right asymmetry disorders and presents as internal organ reversal or randomization. Up to date, at least 82 genes have been identified as the causative genetic factors of left-right asymmetry disorders. This study sought to discover potential pathogenic variants responsible for left-right asymmetry disorder present in a Han-Chinese family using whole exome sequencing combined with Sanger sequencing. Novel compound heterozygous variants, c.5690A>G (p.Asn1897Ser) and c.7759G>A (p.Val2587Met), in the dynein axonemal heavy chain 1 gene (DNAH1), were found in the proband and absent in unaffected family members. Conservation analysis has shown that the variants affect evolutionarily conserved residues, which may impact the tertiary structure of the DNAH1 protein. The novel compound heterozygous variants may potentially bear responsibility for left-right asymmetry disorder, which results from a perturbation of left-right axis coordination at the earliest embryonic development stages. This study broadens the variant spectrum of left-right asymmetry disorders and may be helpful for genetic counseling and healthcare management for the diagnosed individual, and promotes a greater understanding of the pathophysiology.

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“…Candidate variants were validated by Sanger sequencing. A co-segregation analysis between possible causative variants and this family's HTX phenotype was performed [19]. Paired primer sequences for the candidate variants (c.3426-1G>A and c.4306C>T) in the DNAH11 gene were synthesized respectively as follows: 5 0 -TGTTGCCAGTTTCATGATAGAGA-3 0 and 5 0 -TACAGCCAGAAGATGCACCA-3 0 ; 5 0 -TTCACCAGCCTTTAGGCAAA-3 0 and 5 0 -TCTCAG TCCCCAGCTCTTTC-3 0 .…”

Section: Sanger Sequencing Variant Analysis and Protein Structure Modelingmentioning

confidence: 99%

DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease

et al. 2021

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Heterotaxy (HTX), a condition characterized by internal organs not being arranged as expected relative to each other and to the left-right axis, is often accompanied with congenital heart disease (CHD). The purpose was to detect the pathogenic variants in a Chinese family with HTX and CHD. A non-consanguineous Han Chinese family with HTX and CHD, and 200 unrelated healthy subjects were enlisted. Exome sequencing and Sanger sequencing were applied to identify the genetic basis of the HTX family. Compound heterozygous variants, c.3426-1G>A and c.4306C>T (p.(Arg1436Trp)), in the dynein axonemal heavy chain 11 gene (DNAH11) were identified in the proband via exome sequencing and further confirmed by Sanger sequencing. Neither c.3426-1G>A nor c.4306C>T variant in the DNAH11 gene was detected in 200 healthy controls. The DNAH11 c.3426-1G>A variant was predicted as altering the acceptor splice site and most likely affecting splicing. The DNAH11 c.4306C>T variant was predicted to be damaging, which may reduce the phenotype severity. The compound heterozygous variants, c.3426-1G>A and c.4306C>T, in the DNAH11 gene might be the pathogenic alterations resulting in HTX and CHD in this family. These findings broaden the variant spectrum of the DNAH11 gene and increase knowledge used in genetic counseling for the HTX family.

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GJB2 c.235delC variant associated with autosomal recessive nonsyndromic hearing loss and auditory neuropathy spectrum disorder

Cited by 9 publications

References 19 publications

Screening Copy Number Variations in 35 unsolved Inherited Retinal Disease Families

Screening Copy Number Variations in 35 unsolved Inherited Retinal Disease Families

Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder

DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease

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