Incomplete penetrance of MITF gene c.943C&gt;T mutation in an extended family with Waardenburg syndrome type II

Alehabib, Elham; Alinaghi, Somayeh; Pourfatemi, Fatemeh; Darvish, Hossein

doi:10.1016/j.ijporl.2020.110014

Cited by 7 publications

(6 citation statements)

References 12 publications

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“…Heterozygous variants in MITF also show incomplete penetrance in WS families (Yan et al, 2011 ). However, incomplete penetrance of MITF in WS2 is rare, first reported by Alehabib et al, ( 2020 ) Our patients in family 4 carried the same MITF mutation, but had different symptoms. We postulate that different genetic backgrounds, environmental factors, stochastic events, modifying genes, and epigenetics play a role in the penetrance of hearing loss (Pingault et al, 2010 ).…”

Section: Discussionmentioning

confidence: 51%

Identification of novel MITF mutations in Chinese families with Waardenburg syndrome type II

Wang

Yan

et al. 2021

Molec Gen & Gen Med

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Background Waardenburg syndrome (WS) is a rare autosomal‐dominant syndrome and is characterized by sensorineural hearing loss and pigment abnormalities. It is subdivided into four types according to the clinical characteristics. MITF is one of the major pathogenic genes for type II. The aim of this study was to investigate MITF mutations and the clinical characteristics of WS type 2 (WS2) in four Chinese families. Method Clinical diagnoses were based on detailed clinical findings. Six WS2 patients from four unrelated Chinese families were enrolled. Massively parallel DNA sequencing was used to find pathogenic genes and Sanger sequencing was used to confirm the variants detected. Results Sensorineural hearing loss was observed in four of six patients, three had heterochromia iridis, and five have freckled faces. We identified three novel MITF heterozygous mutations (c.831dupC, c.650G>A, and c.711‐2A>G) and one recurrent heterozygous mutation (c.328C>T) in the four WS2 families. Intra‐familial phenotypic variability and incomplete penetrance were found in WS2 patients with pathogenic variants of MITF. Conclusion Genetic diagnosis was performed for the involved four families based on the clinical manifestations. Four heterozygous mutations were identified in the MITF gene. Our findings expanded the phenotypic and genotypic spectrum of WS.

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Section: Discussionmentioning

confidence: 51%

Identification of novel MITF mutations in Chinese families with Waardenburg syndrome type II

Wang

Yan

et al. 2021

Molec Gen & Gen Med

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“…A three-generation family from North of Iran with the same mutation c.1066 C > T, with 9 people with WS2 and 4 normal carriers was reported [17]. We have not found any genetic alterations in all living relatives, but the genetic study was not possible in the paternal grandparents because they were dead at the time of the study, so it could not be ruled out that the mutation was de novo or inherited.…”

Section: Discussionmentioning

confidence: 81%

A Nonsense MITF Mutation Associated with Autosomal Dominant Hearing Loss and Intra-Family Clinical Heterogeneity

Venegas¹,

Boronat

Luna

et al. 2021

BJSTR

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involving hearing loss includes Branchio-Oto-Renal syndrome, ARTICLE INFO ABSTRACTObjectives: Hearing loss is the most common sensory disorder in humans. Approximately 60% of cases of congenital hearing loss have a genetic aetiology. Consequently, the genetic study would significantly improve the diagnostic performance of these hearing impairments avoiding unnecessary tests and helping to establish the evolution, prognosis and treatment of the disease. These studies are of great relevance in cases of syndromic hearing loss.Methods: Using an own designed panel of next generation sequencing (NGS), we studied the case of a two year old boy, with a congenital bilateral NSHL detected through neonatal hearing screening. The patient did not present any other associated pathology. As the hearing loss was profound and bilateral, it was decided to place a cochlear implant in both ears when he was one year old. Results:The analysis revealed the presence of the heterozygous mutation c.1066C>T, p. (Arg356*), in the MITF (NM_198159.2) gene which was confirmed by Sanger sequencing. The segregation study of the mutation in the MITF gene was performed in the family and only the father showed the same mutation with a different phenotype. Conclusion:We describe the clinical spectrum in a family with MITF mutation. They are a clear example of incomplete intrafamilial penetrance and variable expressivity already reported in other cases with MITF mutations.

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“…In humans, about 15% of WS2 patients possess MITF variants [2]. Some studies have described variable phenotypes and incomplete penetrance of each symptom in multiplex families [10, 69], as was observed in the WSF-13 and WSF-14 families (Figure 2). The mild or absent manifestations of WS in individuals with MITF variants suggest that other modifying factors may affect the disease’s expression [10].…”

Section: Discussionmentioning

confidence: 96%

Identification of eight novel variants acrossPAX3, SOX10, EDNRBandMITFgenes in Waardenburg syndrome with next-generation sequencing

Lee

Chen

et al. 2022

Preprint

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Background: Waardenburg syndrome (WS) is a hereditary, genetically heterogeneous disorder characterized by variable presentations of sensorineural hearing impairment and pigmentation anomalies. Objective: This study aimed to investigate the clinical features of WS in detail and determine the genetic causes of patients with clinically suspected WS. Methods: A total of 24 patients from 21 Han Taiwanese families were enrolled and underwent comprehensive physical and audiological examination. We applied targeted next-generation sequencing (NGS) to investigate the potential causative variants in these patients and further validated the candidate variants through Sanger sequencing. Results: We identified 18 causative variants of WS in our cohort. Of these variants, eight were novel and discovered in PAX3, SOX10, EDNRB, MITF genes, including missense, nonsense, deletion, and splice site variants. Several patients presented skeletal deformities, hypotonia, megacolon, and neurological disorders that were rarely seen in WS. Conclusion: This study revealed highly phenotypic variability in Taiwanese WS patients and demonstrated that targeted NGS allowed us to clarify the genetic diagnosis and extend the genetic variant spectrum of WS.

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Incomplete penetrance of MITF gene c.943C>T mutation in an extended family with Waardenburg syndrome type II

Cited by 7 publications

References 12 publications

Identification of novel MITF mutations in Chinese families with Waardenburg syndrome type II

Identification of novel MITF mutations in Chinese families with Waardenburg syndrome type II

A Nonsense MITF Mutation Associated with Autosomal Dominant Hearing Loss and Intra-Family Clinical Heterogeneity

Identification of eight novel variants acrossPAX3, SOX10, EDNRBandMITFgenes in Waardenburg syndrome with next-generation sequencing

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