Building platelet phenotypes: Diaphanous-related formin 1 (DIAPH1)-related disorder

Rabbolini, David J.; Liang, Hai; Connor, David; Whittaker, Shane; Dunkley, Scott; Donikian, Dea; Kondo, Mayuko; Chen, Walter; Stevenson, William; Campbell, Heather; Joseph, Joanne; Ward, Christopher; Brighton, Timothy; Chen, Vivien

doi:10.1080/09537104.2021.1937593

Cited by 4 publications

(4 citation statements)

References 49 publications

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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%

“…Variants in other domains are also predicted to be disruptive for autoinhibition [Kim et al, 2019;Kang et al, 2017]. Consequent uncontrolled F-actin polymerization may lead to an abnormal cytoskeleton in the hair cells and macrothrombocytes [Lakha et al, 2021;Rabbolini et al, 2022], disturbing their proper function. Interestingly, some studied variants retain autoinhibitory activity (c.793G>T, c.1589T>G, c.3661+1G>T), while others do not (c.3610C>T, c.3637C>T, c.3624_3625del) [Ueyama et al, 2016;Lakha et al, 2021].…”

Section: Diaph1mentioning

confidence: 99%

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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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Section: Diaph1mentioning

confidence: 99%

Section: Diaph1mentioning

confidence: 99%

Monogenic Causes of Low-Frequency Non-Syndromic Hearing Loss

et al. 2023

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“…Despite being an autosomal dominant disease, MYH9 ‐related diseases may have a negative family history since some patients may have de novo MYH9 mutations. It is worth noting that patients with diaphanous‐related formin 1 ( DIAPH1 ) mutation‐related macrothrombocytopenia also have sensorineural hearing loss, 24 which overlaps with clinical features of MYH9 ‐related diseases.…”

Section: Congenital Thrombocytopeniamentioning

confidence: 99%

Platelet genetic testing by next‐generation sequencing: A practical update

Chen

Pruthi

2023

Int J Lab Hematology

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Inherited platelet disorders (IPDs) are a heterogeneous group of disorders characterized by normal or reduced platelet counts, bleeding diatheses of varying severities, and the presence (syndromic) or absence (non‐syndromic) of involvement of other organs. Due to the lack of highly specific platelet function tests and overlapping clinical and laboratory features, diagnosing the underlying cause of IPDs remains challenging. In recent years, genetic testing via next‐generation sequencing (NGS) technologies to rapidly analyze multiple genes has gradually emerged as an important part of the laboratory investigation of patients with IPDs. A systemic clinical and laboratory testing approach and thorough phenotype and genotype correlation studies of both patients and their family members are crucial for accurate diagnoses of IPDs.

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“…11 This is also true in humans since alterations of the Diaphanous-Related Formin 1 (DIAPH-1) gene have recently been reported to be responsible for inherited macrothrombocytopenia. 12 Moreover, actin interacts with spectrin, below the platelets' membrane, to ensure the discoid shape of resting platelets and is also distributed within the cytoplasm in a tight net for the distribution of granules in the vicinity of tubulin microtubules. Dysregulation of these two meshes through mutation of the ACTB gene could be responsible for the disordered "swirling" images observed in microscopy, also reported by Latham et al 5 This could have been evidenced by electron microscopy which, unfortunately was not available for this patient.…”

mentioning

confidence: 99%

The identification of giant platelets with disorganized granules can suggest ACTB gene mutation

Fouassier

Isidor

Cogné

et al. 2022

Int J Lab Hematology

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Actinomyopathy-associated syndromic thrombocytopenia (ACTB-AST) is a recently described syndrome associated with congenital anomalies of the beta-actin gene, ACTB. There are six isoforms of actin in humans of which only two are present in nonmuscle tissues: cytoplasmic actin beta (β-CYA) and cytoplasmic actin gamma. 1 β-CYA is involved in cell contractility and intercellular contacts. 2,3 It is also the isoform present in nuclei. 4 Sequence variants located in exons 5 and 6 of the ACTB gene (that encodes β-CYA) have been shown to

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Building platelet phenotypes: Diaphanous-related formin 1 (DIAPH1)-related disorder

Cited by 4 publications

References 49 publications

Monogenic Causes of Low-Frequency Non-Syndromic Hearing Loss

Monogenic Causes of Low-Frequency Non-Syndromic Hearing Loss

Platelet genetic testing by next‐generation sequencing: A practical update

The identification of giant platelets with disorganized granules can suggest ACTB gene mutation

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