A deleterious mutation in the <i>LOXHD1</i> gene causes autosomal recessive hearing loss in Ashkenazi Jews

Edvardson, Simon; Jalas, Chaim; Shaag, Avraham; Zenvirt, Shamir; Landau, Carmit; Lerer, Israela; Elpeleg, Orly

doi:10.1002/ajmg.a.33972

Cited by 30 publications

(33 citation statements)

References 12 publications

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“…Vozzi et al reported three patients, in a consanguineous family, who had early-onset progressive SNHL, which was differed in degree in spite of having the same genotype; homozygous nonsense alleles (c.1588G>T, p.E530X) [3]. On the other hand, non-progressive congenital SNHL was also reported in other homozygous nonsense alleles (c.4714C>T, p.R1572X) [4]. In samba mice, a homozygous missense mutation in Loxhd1 caused profound deafness shortly after birth.…”

Section: Discussionmentioning

confidence: 99%

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Mutations in LOXHD1 Gene Cause Various Types and Severities of Hearing Loss

Mori

Moteki

Kobayashi

et al. 2015

Ann Otol Rhinol Laryngol

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Objective We present two families that were identified with novel mutations in LOXHD1, as a cause of non-progressive hearing loss. Methods One thousand three hundred fourteen (1,314) Japanese subjects with sensorineural hearing loss from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known non-syndromic hearing loss genes were performed to identify the genetic cause of hearing loss. Results Two patients in one family affected with homozygous mutation; c.879+1G>A in LOXHD1, showed profound congenital hearing loss, whereas two patients in the other family with compound heterozygous mutations; c.5869G>T (p.E1957X) and c.4480C>T (p.R1494X) showed moderate to severe hearing loss. Conclusion Mutations in LOXHD1 are extremely rare, and these cases are the first identified in a Japanese population. The genotype-phenotype correlation in LOXHD1 is still unclear. The differences of phenotypes in each patient might be the result of the nature of the mutations, or the location at the gene, or be influenced by genetic modifier.

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Section: Discussionmentioning

confidence: 99%

“…SNHL, caused by the mutations in LOXHD1 , had a phenotypic feature showing progressive hearing loss at mid to high frequencies during childhood [2,3]. On the other hand, non-progressive congenital profound hearing loss has been reported as well [4]. …”

Section: Introductionmentioning

confidence: 99%

Mutations in LOXHD1 Gene Cause Various Types and Severities of Hearing Loss

Mori

Moteki

Kobayashi

et al. 2015

Ann Otol Rhinol Laryngol

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“…This could either lead to a protein lacking 10 PLAT domains or nonsense mediated decay of the transcript could lead to absence of LOXHD1. In contrast, the only other mutation reported in LOXHD1 is a founder mutation, p.R1572X, in the Ashkenazi Jews and causes prelingual profound degree of deafness (Edvardson et al, 2011).…”

Section: Loxhd1 (Dfnb77)mentioning

confidence: 95%

Genetics of Nonsyndromic Recessively Inherited Moderate to Severe and Progressive Deafness in Humans

Naz¹

2012

Hearing Loss

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“…These genes include GJB6, PCDH15, USH1C, MYO3A, SLC26A4, LOXHD1, CDH23, MYO15A, WFS1, TECTA, POU4F3 and the inverted duplication of TJP2. 3,[23][24][25] All known deafness-causing mutations in the Palestinian population were excluded, including mutations in CDH23, MYO7A, MYO15A, OTOF, PJVK, SLC26A4, TECTA, TMHS, TMPRSS3, OTOA, PTPRQ and GPSM2. 22,26,27 Massive parallel sequencing Capture libraries were created and MPS was performed, followed by bioinformatics analysis, as previously described.…”

Section: Gene Exclusionmentioning

confidence: 99%

Novel myosin mutations for hereditary hearing loss revealed by targeted genomic capture and massively parallel sequencing

et al. 2013

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Hereditary hearing loss is genetically heterogeneous, with a large number of genes and mutations contributing to this sensory, often monogenic, disease. This number, as well as large size, precludes comprehensive genetic diagnosis of all known deafness genes. A combination of targeted genomic capture and massively parallel sequencing (MPS), also referred to as next-generation sequencing, was applied to determine the deafness-causing genes in hearing-impaired individuals from Israeli Jewish and Palestinian Arab families. Among the mutations detected, we identified nine novel mutations in the genes encoding myosin VI, myosin VIIA and myosin XVA, doubling the number of myosin mutations in the Middle East. Myosin VI mutations were identified in this population for the first time. Modeling of the mutations provided predicted mechanisms for the damage they inflict in the molecular motors, leading to impaired function and thus deafness. The myosin mutations span all regions of these molecular motors, leading to a wide range of hearing phenotypes, reinforcing the key role of this family of proteins in auditory function. This study demonstrates that multiple mutations responsible for hearing loss can be identified in a relatively straightforward manner by targeted-gene MPS technology and concludes that this is the optimal genetic diagnostic approach for identification of mutations responsible for hearing loss.

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A deleterious mutation in the LOXHD1 gene causes autosomal recessive hearing loss in Ashkenazi Jews

Cited by 30 publications

References 12 publications

Mutations in LOXHD1 Gene Cause Various Types and Severities of Hearing Loss

Mutations in LOXHD1 Gene Cause Various Types and Severities of Hearing Loss

Genetics of Nonsyndromic Recessively Inherited Moderate to Severe and Progressive Deafness in Humans

Novel myosin mutations for hereditary hearing loss revealed by targeted genomic capture and massively parallel sequencing

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