TBL1Y: a new gene involved in syndromic hearing loss

Hearing loss (HL) is the most frequent sensory disorder, affecting about 1–3 per 1000 live births, with more than half of the cases attributable to genetic causes. Despite the fact that many HL causative genes have already been identified, current genetic tests fail to provide a diagnosis for about 40% of the patients, suggesting that other causes still need to be discovered. Here, we describe a four-generation Italian family affected by autosomal dominant non-syndromic hearing loss (ADNSHL), in which exome sequencing revealed a likely pathogenic variant in NCOA3 (NM_181659.3, c.2909G>C, p.(Gly970Ala)), a gene recently described as a novel candidate for ADNSHL in a Brazilian family. A comparison between the two families highlighted a series of similarities: both the identified variants are missense, localized in exon 15 of the NCOA3 gene and lead to a similar clinical phenotype, with non-syndromic, sensorineural, bilateral, moderate to profound hearing loss, with a variable age of onset. Our findings (i.e., the identification of the second family reported globally with HL caused by a variant in NCOA3) further support the involvement of NCOA3 in the etiopathogenesis of ADNSHL, which should, thus, be considered as a new gene for autosomal dominant non-syndromic hearing loss.

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New gene for autosomal recessive non-syndromic hearing loss maps to either chromosome 3q or 19p

American Journal of Medical Genetics ◽

10.1002/(sici)1096-8628(19970905)71:4<467::aid-ajmg18>3.0.co;2-e ◽

1997 ◽

Vol 71 (4) ◽

pp. 467-471 ◽

Cited By ~ 27

Author(s):

Achih Chen ◽

Sigrid Wayne ◽

Adam Bell ◽

Arabandi Ramesh ◽

C.R. Srikumari Srisailapathy ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

New Gene ◽

Syndromic Hearing Loss

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Occurrence of del( GIB6 -D13S1830) mutation in italian non-syndromic hearing loss patients carrying a single GJB2 mutated allele

Acta Oto-Laryngologica ◽

10.1080/03655230410017166 ◽

2004 ◽

Vol 124 (0) ◽

pp. 29-34 ◽

Cited By ~ 17

Author(s):

F. Gualandi ◽

A. Ravani ◽

A. Berto ◽

S. Burdo ◽

P. Trevisi ◽

...

Keyword(s):

Hearing Loss ◽

Syndromic Hearing Loss

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Role of Genetic Factors in the Causation of Non-Syndromic Hearing Loss (NSHL) in Indian Population

Archives of Clinical and Biomedical Research ◽

10.26502/acbr.50170143 ◽

2020 ◽

Vol 04 (06) ◽

Author(s):

Shehnaz Sultana ◽

Pratibha Nallari ◽

Venkateshwari Ananthapur

Keyword(s):

Hearing Loss ◽

Indian Population ◽

Genetic Factors ◽

Syndromic Hearing Loss

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Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

International Journal of Molecular Sciences ◽

10.3390/ijms22126497 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6497

Author(s):

Anna Ghilardi ◽

Alberto Diana ◽

Renato Bacchetta ◽

Nadia Santo ◽

Miriam Ascagni ◽

...

Keyword(s):

Hearing Loss ◽

Inner Ear ◽

Hair Cells ◽

Muscle Fibers ◽

Underlying Mechanism ◽

Loss Of Function ◽

Zebrafish Model ◽

Developmental Defects ◽

Inner Ear Development ◽

Syndromic Hearing Loss

The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear development. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.

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Lights and Shadows in the Genetics of Syndromic and Non-Syndromic Hearing Loss in the Italian Population

Genes ◽

10.3390/genes11111237 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1237

Author(s):

Anna Morgan ◽

Stefania Lenarduzzi ◽

Beatrice Spedicati ◽

Elisabetta Cattaruzzi ◽

Flora Maria Murru ◽

...

Keyword(s):

Hearing Loss ◽

Disease Genes ◽

Italian Population ◽

Essential Information ◽

Whole Exome ◽

Relevant Role ◽

Multiplex Ligation Probe Amplification ◽

Syndromic Hearing Loss

Hearing loss (HL), both syndromic (SHL) and non-syndromic (NSHL), is the most common sensory disorder, affecting ~460 million people worldwide. More than 50% of the congenital/childhood cases are attributable to genetic causes, highlighting the importance of genetic testing in this class of disorders. Here we applied a multi-step strategy for the molecular diagnosis of HL in 125 patients, which included: (1) an accurate clinical evaluation, (2) the analysis of GJB2, GJB6, and MT-RNR1 genes, (3) the evaluation STRC-CATSPER2 and OTOA deletions via Multiplex Ligation Probe Amplification (MLPA), (4) Whole Exome Sequencing (WES) in patients negative to steps 2 and 3. Our approach led to the characterization of 50% of the NSHL cases, confirming both the relevant role of the GJB2 (20% of cases) and STRC deletions (6% of cases), and the high genetic heterogeneity of NSHL. Moreover, due to the genetic findings, 4% of apparent NSHL patients have been re-diagnosed as SHL. Finally, WES characterized 86% of SHL patients, supporting the role of already know disease-genes. Overall, our approach proved to be efficient in identifying the molecular cause of HL, providing essential information for the patients’ future management.

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Novel MYO15A variants are associated with hearing loss in the two Iranian pedigrees

BMC Medical Genetics ◽

10.1186/s12881-020-01168-x ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Somayeh Khatami ◽

Masomeh Askari ◽

Fatemeh Bahreini ◽

Morteza Hashemzadeh-Chaleshtori ◽

Saeed Hematian ◽

...

Keyword(s):

Hearing Loss ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Genetic Diagnosis ◽

Clinical Genetic ◽

Large Size ◽

Whole Exome ◽

Novel Variants ◽

Syndromic Hearing Loss ◽

Traditional Approaches

Abstract Background Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods. Methods This study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families. Results The results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) disease-causing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects. Conclusion In this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL.

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