&lt;b&gt;&lt;i&gt;DIAPH1&lt;/i&gt;&lt;/b&gt; Mutation as a Novel Cause of Autosomal Dominant Macrothrombocytopenia and Hearing Loss

Karki, Nabin Raj; Ajebo, Germame; Savage, Natasha M.; Kutlar, Abdullah

doi:10.1159/000506727

Cited by 7 publications

(5 citation statements)

References 8 publications

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“…In this disorder, auditory loss generally starts during the first decade of life, although there are cases with intrafamilial variability. Since the identification of a mutation in DIAPH1 as the cause of sensorineural hearing loss in a large Costa Rican family [6], more families with a dominant pedigree caused by DIAPH1 mutation have been described elsewhere in the world [11][12][13]18,19,[21][22][23][24][25][26][27]. Affected individuals present frameshift or nonsense mutations or deletions near the DAD.…”

Section: Hearing Lossmentioning

confidence: 99%

Formins in Human Disease

Labat-de-Hoz

Alonso

2021

Cells

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Almost 25 years have passed since a mutation of a formin gene, DIAPH1, was identified as being responsible for a human inherited disorder: a form of sensorineural hearing loss. Since then, our knowledge of the links between formins and disease has deepened considerably. Mutations of DIAPH1 and six other formin genes (DAAM2, DIAPH2, DIAPH3, FMN2, INF2 and FHOD3) have been identified as the genetic cause of a variety of inherited human disorders, including intellectual disability, renal disease, peripheral neuropathy, thrombocytopenia, primary ovarian insufficiency, hearing loss and cardiomyopathy. In addition, alterations in formin genes have been associated with a variety of pathological conditions, including developmental defects affecting the heart, nervous system and kidney, aging-related diseases, and cancer. This review summarizes the most recent discoveries about the involvement of formin alterations in monogenic disorders and other human pathological conditions, especially cancer, with which they have been associated. In vitro results and experiments in modified animal models are discussed. Finally, we outline the directions for future research in this field.

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Section: Hearing Lossmentioning

confidence: 99%

Formins in Human Disease

Labat-de-Hoz

Alonso

2021

Cells

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“…Audiograms of our proband and family members showed a typical U-shape. Autosomal dominant deafness caused by mutations in the DIAPH1 gene can be associated with thrombocytopenia [76,77]. However, our family was lost in follow-up, and therefore we cannot rule out this phenotype.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss

Pavlenkova

Varga

Borecka

et al. 2021

Preprint

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The genetic heterogeneity of sensorineural hearing loss (SNHL) is a major hurdle to the detection of disease-causing variants. We aimed to identify underlying causal genes associated with mid-frequency hearing loss (HL), which contributes to less than about 1% of SNHL cases, by whole exome sequencing (WES). Thirty families segregating mid-frequency SNHL, in whom biallelic GJB2 mutations had been previously excluded, were selected from among 851 families in our DNA repository of SNHL. DNA samples from the probands were subjected to WES analysis and searched for candidate variants associated with SNHL. We were able to identify the genetic aetiology in six probands (20%). In total, we found three pathogenic and three likely pathogenic variants in four genes COL4A5, OTOGL, TECTA, TMPRSS3). One proband was a compound heterozygote for a pathogenic variant and a variant of uncertain significance (VUS) in MYO15A gene. To date, MYO15A and TMPRSS3 have not yet been described in association with mid-frequency SNHL. In eight additional probands, eight candidate VUS variants were detected in five genes (DIAPH1, MYO7A, TECTA, TMC1, TSPEAR). Seven of these 16 variants have not yet been published or mentioned in the available databases. The most prevalent gene was TECTA, identified in 23% of all tested families. Furthermore, we confirmed the hypothesis that a substantive portion of cases with this conspicuous audiogram shape is a consequence of a genetic disorder.

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“…The same audiological profile has not been repeated in other families with deafness and variants in DIAPH1usually, this type of HL starts at high frequencies and progresses rapidly. It is usually accompanied by mild macrothrombocytopenia (MTP) and mild neutropenia, suggesting a syndromic character of the DIAPH1-caused HL [Stritt et al, 2016;Ganaha et al, 2017;Neuhaus et al, 2017;Bastida et al, 2018;Westbury et al, 2018;Karki et al, 2021;Rabbolini et al, 2022]. Later, it was found that the low-frequency HL phenotype in the Costa Rican family might have been associated with endolymphatic hydrops, found in one of the family members [Lalwani et al, 1998].…”

Section: Diaph1mentioning

confidence: 99%

Monogenic Causes of Low-Frequency Non-Syndromic Hearing Loss

et al. 2023

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Background: Low-frequency non-syndromic hearing loss (LFNSHL) is a rare form of hearing loss (HL). It is defined as HL at low frequencies (≤2,000 Hz) resulting in a characteristic ascending audiogram. LFNSHL is usually diagnosed postlingually and is progressive, leading to HL affecting other frequencies as well. Sometimes it occurs with tinnitus. Around half of the diagnosed prelingual HL cases have a genetic cause and it is usually inherited in an autosomal recessive mode. Postlingual HL caused by genetic changes generally has an autosomal dominant pattern of inheritance and its incidence remains unknown. Summary: To date, only a handful of genes have been found as causing LFNSHL: well-established WFS1 and, reported in some cases, DIAPH1, MYO7A, TNC, and CCDC50 (respectively, responsible for DFNA6/14/38, DFNA1, DFNA11, DFNA56, and DFNA44). In this review, we set out audiological phenotypes, causative genetic changes, and molecular mechanisms leading to the development of LFNSHL. Key Messages: LFNSHL is most commonly caused by pathogenic variants in the WFS1 gene, but it is also important to consider changes in other HL genes, which may result in similar audiological phenotype.

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<b><i>DIAPH1</i></b> Mutation as a Novel Cause of Autosomal Dominant Macrothrombocytopenia and Hearing Loss

Cited by 7 publications

References 8 publications

Formins in Human Disease

Formins in Human Disease

Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss

Monogenic Causes of Low-Frequency Non-Syndromic Hearing Loss

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