Identification of a Novel Mutation in the Myosin VIIA Motor Domain in a Family with Autosomal Dominant Hearing Loss (DFNA11)

Leva, Francesca Di; D’Adamo, Pio; Cubellis, Maria Vittoria; D’Eustacchio, Angela; Errichiello, Monica; Saulino, Claudio; Auletta, Gennaro; Giannini, Pasquale; Donaudy, Francesca; Ciccodicola, Alfredo; Gasparini, Paolo; Franzè, Annamaria; Marciano, Elio

doi:10.1159/000091199

Cited by 26 publications

(25 citation statements)

References 60 publications

(29 reference statements)

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“…Affected individuals show a bilateral moderate to profound SNHL at all frequencies. 15 The D218N mutation identified in a Chinese DFNA11 family in the present study was implicated in high-frequency hearing loss. A substitution of aspartic acid, a negative charge residue, to neutral asparagine at 218, may have led to loss of hydrogen bonds, thus altering the interchain interactions between the neighboring b-strand, containing residues A230, K231 and D218 (Figures 4a and b).…”

Section: Mutation Analysismentioning

confidence: 55%

“…Only five MYO7A mutations leading to DFNA11 have been reported: p.delA886-K887-K888 in a Japanese pedigree, 7,11 p.G772R in an American pedigree, 12 p.N458I in a Dutch pedigree, 13 p.R853C in a German pedigree 14 and p.A230V in an Italian pedigree. 15 Here, we present the clinical, genetic and molecular characteristics of two large Chinese families with either non-syndromic high-or low-frequency DFNA11. These represent the sixth and seventh DFNA11 families reported to date.…”

Section: Introductionmentioning

confidence: 99%

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Novel missense mutations in MYO7A underlying postlingual high- or low-frequency non-syndromic hearing impairment in two large families from China

et al. 2010

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The myosin VIIA (MYO7A) gene encodes a protein classified as an unconventional myosin. Mutations within MYO7A can lead to both syndromic and non-syndromic hearing impairment in humans. Among different mutations reported in MYO7A, only five led to non-syndromic sensorineural deafness autosomal dominant type 11 (DFNA11). Here, we present the clinical, genetic and molecular characteristics of two large Chinese DFNA11 families with either high-or low-frequency hearing loss. Affected individuals of family DX-J033 have a sloping audiogram at young ages with high frequency are most affected. With increasing age, all test frequencies are affected. Affected members of family HB-S037 present with an ascending audiogram affecting low frequencies at young ages, and then all frequencies are involved with increasing age. Genome-wide linkage analysis mapped the disease loci within the DFNA11 interval in both families. DNA sequencing of MYO7A revealed two novel nucleotide variations, c.652G4A (p.D218N) and c.2011G4A (p.G671S), in the two families. It is for the first time that the mutations identified in MYO7A in the present study are being implicated in DFNA11 in a Chinese population. For the first time, we tested electrocochleography (ECochG) in a DFNA11 family with low-frequency hearing loss. We speculate that the low-frequency sensorineural hearing loss in this DFNA11 family was not associated with endolymphatic hydrops.

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Section: Mutation Analysismentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Novel missense mutations in MYO7A underlying postlingual high- or low-frequency non-syndromic hearing impairment in two large families from China

et al. 2010

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“…Dominant alleles of MYO7A are associated with nonsyndromic, progressive hearing loss DFNA11 (MIM] 601317) [Liu et al, 1997a;Bolz et al, 2004;Luijendijk et al, 2004;Street et al, 2004;Di Leva et al, 2006]. There are also two recessive alleles of MYO7A reported to be associated with DFNB2 (MIM] 600060) [Liu et al, 1997b;Weil et al, 1997], although this is controversial.…”

Section: Introductionmentioning

confidence: 99%

Mutation spectrum ofMYO7Aand evaluation of a novel nonsyndromic deafnessDFNB2allele with residual function

et al. 2008

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Recessive mutations of MYO7A, encoding unconventional myosin VIIA, can cause either a deaf-blindness syndrome (type 1 Usher syndrome; USH1B) or nonsyndromic deafness (DFNB2). In our study, deafness segregating as a recessive trait in 24 consanguineous families showed linkage to markers for the DFNB2/USH1B locus on chromosome 11q13.5. A total of 23 of these families segregate USH1 due to 17 homozygous mutant MYO7A alleles, of which 14 are novel. One family segregated nonsyndromic hearing loss DFNB2 due to a novel three-nucleotide deletion in an exon of MYO7A (p.E1716del) encoding a region of the tail domain. We hypothesized that DFNB2 alleles of MYO7A have residual myosin VIIA. To address this question we investigated the effects of several mutant alleles by making green fluorescent protein (GFP) tagged cDNA expression constructs containing engineered mutations of mouse Myo7a at codons equivalent to pathogenic USH1B and DFNB2 alleles of human MYO7A. We show that in transfected mouse hair cells an USH1B mutant GFP-myosin VIIa does not localize properly to inner ear hair cell stereocilia. However, a GFP-myosin VIIa protein engineered to have an equivalent DFNB2 mutation to p.E1716del localizes correctly in transfected mouse hair cells. This finding is consistent with the hypothesis that p.E1716del causes a less severe phenotype (DFNB2) than the USH1B-associated alleles because the resulting protein retains some degree of normal function.

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“…Four different mutations of the MYO7A gene have been found to be responsible for the development of DFNB2, and five have been shown to cause DFNA11 [7,[13][14][15][16][17]. A total of 5 mutations have been reported to occur in exons 7, 11, 22 and 28 of the MYO7A gene in Asian patients with nonsyndromic hearing loss and USH1B.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel variants in the Myosin VIIA gene of patients with nonsyndromic hearing loss from Taiwan

Yang

Su³

et al. 2009

International Journal of Pediatric Otorhinolaryngology

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Identification of a Novel Mutation in the Myosin VIIA Motor Domain in a Family with Autosomal Dominant Hearing Loss (DFNA11)

Cited by 26 publications

References 60 publications

Novel missense mutations in MYO7A underlying postlingual high- or low-frequency non-syndromic hearing impairment in two large families from China

Novel missense mutations in MYO7A underlying postlingual high- or low-frequency non-syndromic hearing impairment in two large families from China

Mutation spectrum ofMYO7Aand evaluation of a novel nonsyndromic deafnessDFNB2allele with residual function

Identification of novel variants in the Myosin VIIA gene of patients with nonsyndromic hearing loss from Taiwan

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