Point mutation in the MITF gene causing Waardenburg syndrome type II in a three-generation Indian family

Lalwani, Anil K.; Attaie, Ali; Randolph, Frederick T.; Deshmukh, Dilip; Wang, Cynthia; Mhatre, Anand N.; Wilcox, Edward R.

doi:10.1002/(sici)1096-8628(19981204)80:4<406::aid-ajmg20>3.0.co;2-p

Cited by 27 publications

(8 citation statements)

References 14 publications

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“…Contrary to the small range of USH2A pathogenic variants, MITF pathogenic variants causing Waardenburg syndrome type 2 are diverse and usually private, with only a small number of exceptions [ 18 ], [ 35 ]. One of them is a pathogenic variant c.943C>T (p.Arg315*), which was detected in two unrelated families in our study, and has already been reported in three families originating from Northern Europe [ 16 ], India [ 17 ], and Togo [ 18 ].…”

Section: Discussionsupporting

confidence: 66%

Diagnostic outcomes of exome sequencing in patients with syndromic or non-syndromic hearing loss

et al. 2018

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Hereditary hearing loss (HL) is a common sensory disorder, with an incidence of 1–2 per 1000 newborns, and has a genetic etiology in over 50% of cases. It occurs either as part of a syndrome or in isolation and is genetically very heterogeneous which poses a challenge for clinical and molecular diagnosis. We used exome sequencing to seek a genetic cause in a group of 56 subjects (49 probands) with HL: 32 with non-syndromic non-GJB2 HL and 17 with syndromic HL. Following clinical examination and clinical exome sequencing, an etiological diagnosis was established in 15 probands (15/49; 30%); eight (8/17;47%) from the syndromic group and seven (7/32; 21%) from the non-syndromic non-GJB2 subgroup. Fourteen different (half of them novel) non-GJB2 variants causing HL were found in 10 genes (CHD7, HDAC8, MITF, NEFL, OTOF, SF3B4, SLC26A4, TECTA, TMPRSS3, USH2A) among 13 probands, confirming the genetic heterogeneity of hereditary HL. Different genetic causes for HL were found in a single family while three probands with apparent syndromic HL were found to have HL as a separate clinical feature, distinct from the complex phenotype. Clinical exome sequencing proved to be an effective tool used to comprehensively address the genetic heterogeneity of HL, to detect clinically unrecognized HL syndromes, and to decipher complex phenotypes in which HL is a separate feature and not part of a syndrome.

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Section: Discussionsupporting

confidence: 66%

Diagnostic outcomes of exome sequencing in patients with syndromic or non-syndromic hearing loss

et al. 2018

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“…, a flow diagram of the search process is depicted. Out of the 246 potentially eligible articles based on title and abstract, 73 articles met the inclusion criteria and were included in the analysis . One article fulfilled the inclusion criteria, but was not included in the analysis because the patient suffered from a second genetic disorder that could as well result in HL .…”

Section: Resultsmentioning

confidence: 99%

Hearing loss in Waardenburg syndrome: a systematic review

et al. 2015

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Waardenburg syndrome (WS) is a rare genetic disorder characterized by hearing loss (HL) and pigment disturbances of hair, skin and iris. Classifications exist based on phenotype and genotype. The auditory phenotype is inconsistently reported among the different Waardenburg types and causal genes, urging the need for an up-to-date literature overview on this particular topic. We performed a systematic review in search for articles describing auditory features in WS patients along with the associated genotype. Prevalences of HL were calculated and correlated with the different types and genes of WS. Seventy-three articles were included, describing 417 individual patients. HL was found in 71.0% and was predominantly bilateral and sensorineural. Prevalence of HL among the different clinical types significantly differed (WS1: 52.3%, WS2: 91.6%, WS3: 57.1%, WS4: 83.5%). Mutations in SOX10 (96.5%), MITF (89.6%) and SNAI2 (100%) are more frequently associated with hearing impairment than other mutations. Of interest, the distinct disease-causing genes are able to better predict the auditory phenotype compared with different clinical types of WS. Consequently, it is important to confirm the clinical diagnosis of WS with molecular analysis in order to optimally inform patients about the risk of HL.

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“…Various mutations of the MITF gene can be responsible for WS2A [Tassabehji et al, 1994, 1995; Morell et al, 1997; Lalwani et al, 1998]. Interestingly, the exact equivalent of the mouse Mitf mutation, a deletion of one of a run of four arginine residues, that led to the identification of MITF as causative gene for WS2A in humans was found in a family with a phenotype more resembling Tietz syndrome than classic Waardenburg syndrome [Tassabehji et al, 1995].…”

Section: Summary Of the Fish Resultsmentioning

confidence: 99%

Articular cartilage tissue engineering based on a mechano‐active scaffold made of poly(L‐lactide‐co‐ε‐caprolactone): In vivo performance in adult rabbits

et al. 2010

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Our previous studies showed that a mechano-active scaffold made of poly(L-lactide-co-epsilon-caprolactone) (PLCL) exhibited a high potential to realize the formation of a functional, engineered cartilage in vitro. This animal study therefore was designed to investigate the feasibility of repairing on osteochondral defect with the use of bone marrow-derived mesenchymal stem cells (BMSCs) incorporated with a PLCL scaffold. Rabbit BMSCs, isolated and subsequently cultured in monolayer, were seeded into a porous PLCL scaffold sponge following an implantation onto a full-thickness osteochondral defect (diameter of 4.5 mm, depth of 5 mm) that was artificially created on the medial femoral condyles at a high load-bearing site on a rabbit's knee joint. Time-dependent healing of the defect was evaluated by macroscopic, histological examinations at both 3- and 6-month-implantations, respectively. A PLCL sponge incorporated with BMSCs exhibited sufficient structural support, resulting in new osteochondral tissue regeneration: a physiologically well-integrated subchondral bone formation, a hyaline cartilage-like morphology containing chondrocytes surrounded by abundant cartilaginous matrices. In addition, quantitative biochemical assays also demonstrated high potential for the synthesis of sulfated glycosaminoglycan and collagen, both of which are biomolecules essential to extracelluar matrix in normal cartilage tissue. In contrast, defects filled with cell-free PLCL scaffold or left empty showed a very limited potential for regeneration. Our findings suggest that a composite of PLCL-based sponge scaffold and BMSCs promote the repair of osteochondral defects at high load-bearing sites in adult rabbits.

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Point mutation in the MITF gene causing Waardenburg syndrome type II in a three-generation Indian family

Cited by 27 publications

References 14 publications

Diagnostic outcomes of exome sequencing in patients with syndromic or non-syndromic hearing loss

Diagnostic outcomes of exome sequencing in patients with syndromic or non-syndromic hearing loss

Hearing loss in Waardenburg syndrome: a systematic review

Articular cartilage tissue engineering based on a mechano‐active scaffold made of poly(L‐lactide‐co‐ε‐caprolactone): In vivo performance in adult rabbits

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