Hereditary hearing loss: a 96 gene targeted sequencing protocol reveals novel alleles in a series of Italian and Qatari patients

Vozzi, Diego; Morgan, Anna; Vuckovic, Dragana; D’Eustacchio, Angela; Abdulhadi, Khalid; Rubinato, Elisa; Badii, Ramin; Gasparini, Paolo; Girotto, Giorgia

doi:10.1016/j.gene.2014.03.033

Cited by 48 publications

(48 citation statements)

References 28 publications

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“…Targeted NGS sequencing seems suitable for identification of causative mutations in hearing-loss patients due to many genes involved in its etiology and various mode of inheritance. It was previously reported as efficient in identifying mutations in 33 % [14] or 12.7 % [15] of sensorineural hearing-loss cases.…”

Section: Discussionmentioning

confidence: 99%

TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss

Battelino

Klančar

Kovač

et al. 2015

Eur Arch Otorhinolaryngol

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Nonsyndromic genetic deafness is highly heterogeneous in its clinical presentation, pattern of inheritance and underlying genetic causes. Mutations in TMPRSS3 gene encoding transmembrane serine protease account for <1 % of autosomal recessive nonsyndromic hearing loss (ARNSHL) in Caucasians. Targeted next generation sequencing in the index family with profound deaf parents and a son, and Sanger sequencing of selected TMPRSS3 gene regions in a cohort of thirty-five patients with suspected ARNSHL was adopted. A son and his mother in the index family were homozygous for TMPRSS3 c.208delC (p.His70Thrfs*19) variant. Father was digenic compound heterozygote for the same variant and common GJB2 c.35delG variant. Three additional patients from the ARNSHL cohort were homozygous for TMPRSS3 c.208delC. TMPRSS3 defects seem to be an important cause of ARNSHL in Slovenia resulting in uniform phenotype with profound congenital hearing loss, and satisfactory hearing and speech recognition outcome after cochlear implantation. Consequently, TMPRSS3 gene analysis should be included in the first tier of genetic investigations of ARNSHL along with GJB2 and GJB6 genes.

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Section: Discussionmentioning

confidence: 99%

TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss

Battelino

Klančar

Kovač

et al. 2015

Eur Arch Otorhinolaryngol

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“…It played an important role in maintaining normal hair cell function in the cochlea [2]. 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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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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“…Interestingly, after this preliminary screening, the analysis of 4 additional families under investigation was completely negative for the presence of mutations in one of the 96 genes included in the hearing loss panel. This finding implies that other yet unknown HHL genes underlie the disease in these Qatari families [26] .…”

Section: The Role Of Other Genesmentioning

confidence: 78%

“…This elongation does not contain any known motif and is not conserved across species. Immunohistochemistry studies on the mouse inner ear showed Bdp1 expression within the endothelial cells in the stria vascu- Using a targeted re-sequencing approach based on the analysis of 96 HHL genes (including some candidate genes), two additional families have been further characterized at the molecular level [26] . The first one is a consanguineous family, showing bilateral, early-onset, sensorineural hearing impairment, carrying a novel allele in the LOXHD1 gene, which segregates in the homozygous state in all affected family members.…”

Section: The Role Of Other Genesmentioning

confidence: 99%

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Consanguinity and Hereditary Hearing Loss in Qatar

et al. 2014

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Qatar is a sovereign state located on the Eastern coast of the Arabian Peninsula in the Persian Gulf. Its native population consists of 3 major subgroups: people of Arabian origin or Bedouins, those from an Eastern or Persian ancestry and individuals with African admixture. Historically, all types of consanguineous marriages have been and still are common in the Qatari population, particularly among first and double-first cousins. Thus, there is a higher risk for most inherited diseases including hereditary hearing loss (HHL). In particular, a hearing loss prevalence of 5.2% has been reported in Qatar, with parental consanguinity being more common among affected individuals as compared with unaffected ones. Our recent molecular results confirm a high homogeneity and level of inbreeding in Qatari HHL patients. Among all HHL genes, GJB2, the major player worldwide, accounts for a minor proportion of cases and at least 3 additional genes have been found to be mutated in Qatari patients. Interestingly, one gene, BDP1, has been described to cause HHL only in this country. These results point towards an unexpected level of genetic heterogeneity despite the high level of inbreeding. This review provides an up-to-date picture of HHL in Qatar and of the impact of consanguinity on this disease.

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Hereditary hearing loss: a 96 gene targeted sequencing protocol reveals novel alleles in a series of Italian and Qatari patients

Cited by 48 publications

References 28 publications

TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss

TMPRSS3 mutations in autosomal recessive nonsyndromic hearing loss

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

Consanguinity and Hereditary Hearing Loss in Qatar

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