A novel biallelic splice site mutation of TECTA causes moderate to severe hearing impairment in an Algerian family

Behlouli, Asma; Bonnet, Crystel; Abdi, Samia; Hasbellaoui, M.; Boudjenah, Farid; Hardelin, Jean‐Pierre; Louha, Malek; Makrelouf, Mohamed; Ammar-Khodja, Fatima; Zenati, Akila; Petit, Christine

doi:10.1016/j.ijporl.2016.04.040

Cited by 12 publications

(10 citation statements)

References 46 publications

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“…This HL deterioration rate is comparable to the hearing deterioration rate in a normal hearing control population. A previous report stated that patients with TECTA -associated mid-frequency HL might be prone to presbycusis as they are theoretically exposed to a lower level of sound energy as a result of cochlear amplification deficiency [36,37]. However, our results indicated that the hearing loss progression rate was the same as in the control group.…”

Section: Discussioncontrasting

confidence: 71%

The Prevalence and Clinical Characteristics of TECTA-Associated Autosomal Dominant Hearing Loss

Yasukawa

Moteki

Nishio

et al. 2019

Genes

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TECTA is well known as a causative gene for autosomal dominant mid-frequency hearing loss observed in various populations. In this study, we performed next-generation sequencing analysis of a large Japanese hearing loss cohort, including eight hundred and twelve (812) subjects from unrelated autosomal dominant hearing loss families, to estimate the prevalence and phenotype-genotype correlations in patients with TECTA mutations. The prevalence of TECTA mutations in Japanese autosomal dominant sensorineural hearing loss families was found to be 3.2%. With regard to the type of hearing loss, the patients with mutations in the nidogen-like domain or ZA domain of TECTA showed varied audiograms. However, most of the patients with mutations in the ZP domain showed mid-frequency hearing loss. The rate of hearing deterioration in TECTA-associated hearing loss patients and in the normal hearing Japanese control population were the same and regression lines for each group were parallel. We carried out haplotype analysis for four families which had one recurring missense variant, c.5597C>T (p.Thr1866Met). Our results revealed four different haplotypes, suggesting that this mutation occurred independently in each family. In conclusion, TECTA variants represent the second largest cause of autosomal dominant sensorineural hearing loss in Japan. The hearing loss progression observed in the patients with TECTA mutations might reflect presbycusis. The c.5597C>T mutation occurred in a mutational hot spot and is observed in many ethnic populations.

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Section: Discussioncontrasting

confidence: 71%

The Prevalence and Clinical Characteristics of TECTA-Associated Autosomal Dominant Hearing Loss

Yasukawa

Moteki

Nishio

et al. 2019

Genes

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“…Pre-lingual hearing impairment was common in our study population which agrees with other findings (Chibisova et al, 2018). Majority of pre-lingual HI are congenital and are usually caused by genetic factors (Wonkam et al, 2013; Behlouli et al, 2016). Waardenburg syndrome was the most common syndromic HI identified among the congenital cases in line with other African data (Noubiap et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

GJB2 and GJB6 Mutations in Non-Syndromic Childhood Hearing Impairment in Ghana

et al. 2019

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Our study aimed to investigate GJB2 (connexin 26) and GJB6 (connexin 30) mutations associated with non-syndromic childhood hearing impairment (HI) as well as the environmental causes of HI in Ghana. Medical reports of 1,104 students attending schools for the deaf were analyzed. Families segregating HI, as well as isolated cases of HI of putative genetic origin were recruited. DNA was extracted from peripheral blood followed by Sanger sequencing of the entire coding region of GJB2. Multiplex PCR and Sanger sequencing were used to analyze the prevalence of GJB6-D3S1830 deletion. Ninetyseven families segregating HI were identified, with 235 affected individuals; and a total of 166 isolated cases of putative genetic causes, were sampled from 11 schools for the deaf in Ghana. The environmental factors, particularly meningitis, remain a major cause of HI impairment in Ghana. The male/female ratio was 1.49. Only 59.6% of the patients had their first comprehensive HI test between 6 to 11 years of age. Nearly all the participants had sensorineural HI (99.5%; n = 639). The majority had pre-lingual HI (68.3%, n = 754), of which 92.8% were congenital. Pedigree analysis suggested autosomal recessive inheritance in 96.9% of the familial cases. GJB2-R143W mutation, previously reported as founder a mutation in Ghana accounted for 25.9% (21/81) in the homozygous state in familial cases, and in 7.9% (11/140) of non-familial non-syndromic congenital HI cases, of putative genetic origin. In a control population without HI, we found a prevalent of GJB2-R143W carriers of 1.4% (2/145), in the heterozygous state. No GJB6-D3S1830 deletion was identified in any of the HI patients. GJB2-R143W mutation accounted for over a quarter of familial non-syndromic HI in Ghana and should be investigated in clinical practice. The large connexin 30 gene deletion (GJB6-D3S1830 deletion) does not account for of congenital non-syndromic HI in Ghana. There is a need to employ next generation sequencing approaches and functional genomics studies to identify the other genes involved in most families and isolated cases of HI in Ghana.

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“…Recessively inherited defects of TECTA can cause moderate-tosevere HI, although with a more flat audiogram configuration than observed in the presented families. 38,39 We scrutinized TECTA for defects in family W05-682, and we excluded (potentially) causative variants in the exonic sequences and splice sites of the gene. We did not obtain any indication for aberrant splicing that might result from deep intronic variants.…”

Section: Discussionmentioning

confidence: 99%

MPZL2, Encoding the Epithelial Junctional Protein Myelin Protein Zero-like 2, Is Essential for Hearing in Man and Mouse

Wesdorp

Murillo-Cuesta

Peters³

et al. 2018

The American Journal of Human Genetics

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In a Dutch consanguineous family with recessively inherited nonsyndromic hearing impairment (HI), homozygosity mapping combined with whole-exome sequencing revealed a MPZL2 homozygous truncating variant, c.72del (p.Ile24Metfs22). By screening a cohort of phenotype-matched subjects and a cohort of HI subjects in whom WES had been performed previously, we identified two additional families with biallelic truncating variants of MPZL2. Affected individuals demonstrated symmetric, progressive, mild to moderate sensorineural HI. Onset of HI was in the first decade, and high-frequency hearing was more severely affected. There was no vestibular involvement. MPZL2 encodes myelin protein zero-like 2, an adhesion molecule that mediates epithelial cell-cell interactions in several (developing) tissues. Involvement of MPZL2 in hearing was confirmed by audiometric evaluation of Mpzl2-mutant mice. These displayed early-onset progressive sensorineural HI that was more pronounced in the high frequencies. Histological analysis of adult mutant mice demonstrated an altered organization of outer hair cells and supporting cells and degeneration of the organ of Corti. In addition, we observed mild degeneration of spiral ganglion neurons, and this degeneration was most pronounced at the cochlear base. Although MPZL2 is known to function in cell adhesion in several tissues, no phenotypes other than HI were found to be associated with MPZL2 defects. This indicates that MPZL2 has a unique function in the inner ear. The present study suggests that deleterious variants of Mplz2/MPZL2 affect adhesion of the inner-ear epithelium and result in loss of structural integrity of the organ of Corti and progressive degeneration of hair cells, supporting cells, and spiral ganglion neurons.

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A novel biallelic splice site mutation of TECTA causes moderate to severe hearing impairment in an Algerian family

Cited by 12 publications

References 46 publications

The Prevalence and Clinical Characteristics of TECTA-Associated Autosomal Dominant Hearing Loss

The Prevalence and Clinical Characteristics of TECTA-Associated Autosomal Dominant Hearing Loss

GJB2 and GJB6 Mutations in Non-Syndromic Childhood Hearing Impairment in Ghana

MPZL2, Encoding the Epithelial Junctional Protein Myelin Protein Zero-like 2, Is Essential for Hearing in Man and Mouse

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