A novel DFNA5 mutation, IVS8+4 A&gt;G, in the splice donor site of intron 8 causes late‐onset non‐syndromic hearing loss in a Chinese family

Cheng, Jing; Dy, Han; Dai, Peng; Hj, Sun; Tao, Ran; Sun, Qing‐Yuan; Yan, Da; Qin, Wenxin; Hy, Wang; Xm, Ouyang; Sz, Yang; Jy, Cao; Gy, Feng; Li, Du; Yz, Zhang; Sq, Zhai; Wy, Yang; Xz, Liu; He, Lin; Hj, Yuan

doi:10.1111/j.1399-0004.2007.00889.x

Cited by 49 publications

(48 citation statements)

References 10 publications

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“…The N-terminus region of DFNA5 has the same amino acid sequence as the Gsdm family proteins and is referred to as the DFNA5-Gasdermin domain (Delmaghani et al 2006; Tamura et al 2007). Germline mutations in DFNA5 have been discovered in human families and cause autosomal-dominant hearing loss (Van Laer et al 1998; Yu et al 2003; Cheng et al 2007). In many cases, the DFNA5 mutations lead to exon 8 skipping, resulting in frameshift and premature truncation of the protein (Van Laer et al 1998; Yu et al 2003; Cheng et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Functional Conservation of Gsdma Cluster Genes Specifically Duplicated in the Mouse Genome

Tanaka¹,

Mizushina

Kato

et al. 2013

G3 Genes|Genomes|Genetics

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Mouse Gasdermin A3 (Gsdma3) is the causative gene for dominant skin mutations exhibiting alopecia. Mouse has two other Gsdma3-related genes, Gsdma and Gsdma2, whereas human and rat have only one related gene. To date, no skin mutation has been reported for human GSDMA and rat Gsdma as well as mouse Gsdma and Gsdma2. Therefore, it is possible that only Gsdma3 has gain-of-function type mutations to cause dominant skin phenotype. To elucidate functional divergence among the Gsdma-related genes in mice, and to infer the function of the human and rat orthologs, we examined in vivo function of mouse Gsdma by generating Gsdma knockout mice and transgenic mice that overexpress wild-type Gsdma or Gsdma harboring a point mutation (Alanine339Threonine). The Gsdma knockout mice shows no visible phenotype, indicating that Gsdma is not essential for differentiation of epidermal cells and maintenance of the hair cycle, and that Gsdma is expressed specifically both in the inner root sheath of hair follicles and in suprabasal cell layers, whereas Gsdma3 is expressed only in suprabasal layers. By contrast, both types of the transgenic mice exhibited epidermal hyperplasia resembling the Gsdma3 mutations, although the phenotype depended on the genetic background. These results indicate that the mouse Gsdma and Gsdma3 genes share common function to regulate epithelial maintenance and/or homeostasis, and suggest that the function of human GSDMA and rat Gsdma, which are orthologs of mouse Gsdma, is conserved as well.

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Section: Discussionmentioning

confidence: 99%

Functional Conservation of Gsdma Cluster Genes Specifically Duplicated in the Mouse Genome

Tanaka¹,

Mizushina

Kato

et al. 2013

G3 Genes|Genomes|Genetics

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“…All 4 identified mutations result in the skipping of exon 8 of the DFNA5 gene, raising the hypothesis that there is a specific gain-of-function effect [Van Laer et al, 1998Cheng et al, 2007]. Two patients (cases 1 and 3) described by Duno et al [2004] had deletions of the complete DFNA5 gene without hearing loss.…”

Section: Discussionmentioning

confidence: 99%

Severe Developmental Delay in a Patient with 7p21.1–p14.3 Microdeletion Spanning the TWIST Gene and the HOXA Gene Cluster

et al. 2011

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We describe a patient with a rare interstitial deletion of chromosome 7p21.1–p14.3 detected by array-CGH. The deletion encompassed 74 genes and caused haploinsufficiency (or loss of allele) of 6 genes known to be implicated in different autosomal dominant genetic disorders: TWIST, DFNA5, CYCS, HOXA11, HOXA13, and GARS. The patient had several morphological abnormalities similar to Saethre-Chotzen syndrome (caused by TWIST mutations) including craniosynostosis of the coronal suture and anomalies similar to those seen in hand-foot-uterus syndrome (caused by HOXA13 mutations) including hypospadias. The combined phenotype of Saethre-Chotzen syndrome and hand-foot-uterus syndrome of our patient closely resembles a previously reported case with a cytogenetically visible small deletion spanning 7p21–p14.3. We therefore conclude that microdeletions of 7p spanning the TWIST gene and HOXA gene cluster lead to a clinically recognizable ‘haploinsufficiency syndrome’.

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“…At the genomic level, the gene spans 60kB and translates an mRNA transcript of 1491bp. To date, four different genomic mutations have been identified that on the RNA level always lead to skipping of exon 8 (Bischoff et al, 2004; Cheng et al, 2007; Van Laer et al, 1998; Yu et al, 2003). DFNA5 is expressed in all tissues investigated so far, albeit at a low level.…”

Section: Apoptosis In Monogenic Forms Of Hearing Lossmentioning

confidence: 99%

Apoptosis in acquired and genetic hearing impairment: The programmed death of the hair cell

Beeck¹,

Schacht²,

Camp³

2011

Hearing Research

126

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Apoptosis is an important physiological process. Normally, a healthy cell maintains a delicate balance between pro- and anti-apoptotic factors, allowing it to live and proliferate. It is thus not surprising that disturbance of this delicate balance may result in disease. It is a well known fact that apoptosis also contributes to several acquired forms of hearing impairment. Noise-induced hearing loss is the result of prolonged exposure to excessive noise, triggering apoptosis in terminally differentiated sensory hair cells. Moreover, hearing loss caused by the use of therapeutic drugs such as aminoglycoside antibiotics and cisplatin potentially may result in the activation of apoptosis in sensory hair cells leading to hearing loss due to the “ototoxicity” of the drugs. Finally, apoptosis is a key contributor to the development of presbycusis, age-related hearing loss. Recently, several mutations in apoptosis genes were identified as the cause of monogenic hearing impairment. These genes are TJP2, DFNA5 and MSRB3. This implies that apoptosis not only contributes to the pathology of acquired forms of hearing impairment, but also to genetic hearing impairment as well. We believe that these genes constitute a new functional class within the hearing loss field. Here, the contribution of apoptosis in the pathology of both acquired and genetic hearing impairment is reviewed.

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A novel DFNA5 mutation, IVS8+4 A>G, in the splice donor site of intron 8 causes late‐onset non‐syndromic hearing loss in a Chinese family

Cited by 49 publications

References 10 publications

Functional Conservation of Gsdma Cluster Genes Specifically Duplicated in the Mouse Genome

Functional Conservation of Gsdma Cluster Genes Specifically Duplicated in the Mouse Genome

Severe Developmental Delay in a Patient with 7p21.1–p14.3 Microdeletion Spanning the <i>TWIST</i> Gene and the <i>HOXA</i> Gene Cluster

Apoptosis in acquired and genetic hearing impairment: The programmed death of the hair cell

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