A Second Family with Nonsyndromic Sensorineural Hearing Loss Linked to Xp21.2: Refinement of the DFN4 Locus within DMD

Pfister, Markus; Apaydın, Fazıl; Turan, Onur; Bereketoğlu, Mehmet Ali; Bylgen, V; Braendle, Uwe; Zenner, H. P.; Lalwani, Anil K.

doi:10.1006/geno.1998.5538

Cited by 12 publications

(9 citation statements)

References 39 publications

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“…Pfister et al (73) identified a Turkish family with very similar hearing loss as the family described by Lalwani et al (72). The hearing loss was congenital.…”

Section: The Dfn3 Locus-pou3f4 Gene (Omim 304400)mentioning

confidence: 65%

Sex‐linked deafness

Petersen

Wang

Willems³

2007

Clinical Genetics

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Many human syndromes associated with hearing loss are caused by disease genes located on the X chromosome, but few X-linked loci for non-syndromic hearing loss have been reported. Surprisingly, a Y-linked locus has been identified, representing one of the only disease loci on the Y chromosome. This study reviews the different sex-linked genes and loci on the X- and Y chromosome leading to syndromic and especially non-syndromic hearing loss.

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“…Pfister et al (73) identified a Turkish family with very similar hearing loss as the family described by Lalwani et al (72). The hearing loss was congenital.…”

Section: The Dfn3 Locus-pou3f4 Gene (Omim 304400)mentioning

confidence: 65%

Sex‐linked deafness

Petersen

Wang

Willems³

2007

Clinical Genetics

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“…8,9 An additional locus has been mapped to the short arm of the X chromosome (DFNX3, formerly DFN4) overlapping with the DMD locus on Xp21.2. 10,11 Here, we present data on a Hungarian family in which only male subjects suffer from severe congenital hearing loss, whereas female subjects are not or only mildly to moderately affected. Based on the highly suggestive X-linked recessive inheritance and after ruling out the known X-linked genes PRPS1 and POU3F4, next-generation sequencing (NGS) of the X-chromosomal exome was performed on three family members in order to identify the underlying genetic defect.…”

Section: Introductionmentioning

confidence: 99%

Novel form of X-linked nonsyndromic hearing loss with cochlear malformation caused by a mutation in the type IV collagen gene COL4A6

et al. 2013

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Hereditary hearing loss is the most common human sensorineural disorder. Genetic causes are highly heterogeneous, with mutations detected in 440 genes associated with nonsyndromic hearing loss, to date. Whereas autosomal recessive and autosomal dominant inheritance is prevalent, X-linked forms of nonsyndromic hearing impairment are extremely rare. Here, we present a Hungarian three-generation family with X-linked nonsyndromic congenital hearing loss and the underlying genetic defect. Next-generation sequencing and subsequent segregation analysis detected a missense mutation (c.1771G4A, p.Gly591Ser) in the type IV collagen gene COL4A6 in all affected family members. Bioinformatic analysis and expression studies support this substitution as being causative. COL4A6 encodes the alpha-6 chain of type IV collagen of basal membranes, which forms a heterotrimer with two alpha-5 chains encoded by COL4A5. Whereas mutations in COL4A5 and contiguous X-chromosomal deletions involving COL4A5 and COL4A6 are associated with X-linked Alport syndrome, a nephropathy associated with deafness and cataract, mutations in COL4A6 alone have not been related to any hereditary disease so far. Moreover, our index patient and other affected family members show normal renal and ocular function, which is not consistent with Alport syndrome, but with a nonsyndromic type of hearing loss. In situ hybridization and immunostaining demonstrated expression of the COL4A6 homologs in the otic vesicle of the zebrafish and in the murine inner ear, supporting its role in normal ear development and function. In conclusion, our results suggest COL4A6 as being the fourth gene associated with X-linked nonsyndromic hearing loss.

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“…The deafness in this three‐generation family from Turkey with nonsyndromic X‐linked hearing loss maps to DFN4 locus at Xp21.2; the deafness cosegregates with markers located entirely within the DMD gene 11 …”

Section: Methodsmentioning

confidence: 89%

“…This family provides genetic and clinical evidence for an etiologic role of dystrophin in deafness associated with DFN4. Genetically, with the aid of this family, the DFN4 gene is now restricted to a region entirely within the DMD locus 11 . Also, clinical examination of this family further implicates dystrophin dysfunction in hearing loss and is the basis for this report.…”

Section: Introductionmentioning

confidence: 80%