The molecular genetics of Usher syndrome

Ahmed, Zaheer; Riazuddin, Sheikh; Er, Wilcox

doi:10.1034/j.1399-0004.2003.00109.x

Cited by 140 publications

(119 citation statements)

References 102 publications

(174 reference statements)

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“…Mutations in the myosin-VIIa gene cause human Usher disease, characterized by hearing impairment, balance dysfunction and progressive retinal degeneration (Ahmed et al 2003;Weil et al 1995). In the retina, myosin-VIIa is expressed in two adjacent cell types, the photoreceptors and the retinal pigment epithelia (RPE), and of these two cell types, myosinVIIa is most highly expressed in the RPE (Hasson et al 1995;Wolfrum et al 1998).…”

Section: Introductionmentioning

confidence: 99%

The unconventional myosin-VIIa associates with lysosomes

Soni

Warren

Bucci

et al. 2005

Cell Motil. Cytoskeleton

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Mutations in the myosin-VIIa (MYO7a) gene cause human Usher disease, characterized by hearing impairment and progressive retinal degeneration. In the retina, myosin-VIIa is highly expressed in the retinal pigment epithelium, where it plays a role in the positioning of melanosomes and other digestion organelles. Using a human cultured retinal pigmented epithelia cell line, ARPE-19, as a model system, we have found that a population of myosin-VIIa is associated with cathepsin D-and Rab7-positive lysosomes. Association of myosin-VIIa with lysosomes was Rab7 independent, as dominant negative and dominant active versions of Rab7 did not disrupt myosin-VIIa recruitment to lysosomes. Association of myosin-VIIa with lysosomes was also independent of the actin and microtubule cytoskeleton. Myosin-VIIa copurified with lysosomes on density gradients, and fractionation and extraction experiments suggested that it was tightly associated with the lysosome surface. These studies suggest that myosin-VIIa is a lysosome motor.

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Section: Introductionmentioning

confidence: 99%

The unconventional myosin-VIIa associates with lysosomes

Soni

Warren

Bucci

et al. 2005

Cell Motil. Cytoskeleton

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“…Conversely, only deletions or displacements were found in patients with USH1D. 7 Therefore, the type of mutation can have a crucial role in phenotypic expression.…”

Section: Molecular Genetics Of Non-syndromic Hearing Lossmentioning

confidence: 99%

“…12 4) Cadherin-23: it belongs to the family of transmembrane proteins, dependent on Ca 2+ ions, with over 20 different members, making part of a molecular structure of intercellular adhesion junctions or zones of adhesion (zonnula adherens). Chromosome sites for DFNB12 (10q21-q22) 13 and Usher syndrome Type I (USH1D -10q) 7 were mapped in chromosome 10. Gene CDH23, with 69 exons codifies protein cadherin-23 (3354 amino acids) expressed in both cochlear hair cells, promoting strong adhesion between each of their types, maintaining polarization of plasma membrane depending on occlusion junctions (claudin-14 protein) and cytoskeleton.…”

Section: Molecular Genetics Of Non-syndromic Hearing Lossmentioning

confidence: 99%

“…10 2) Harmonin: gene site, if mutant, causes DFNB18, and was mapped at chromosome 11 (11p15.1), at the same gene location as USH1C (Usher Syndrome Type IC11p15.1). 7,11 Gene USH1C (28 exons) codifies a protein that contains domain PDZ, denominated harmonin. At the cochlea, harmonin is restricted to hair cells, in which it is present in the cellular body and stereocilia.…”

Section: Molecular Genetics Of Non-syndromic Hearing Lossmentioning

confidence: 99%

“…Functional characterization of domain corresponding to harmonin protein provides the understanding of the pathogenesis of DFNB18 and USH1C syndrome. 7 3) Villin: protein that belongs to the molecule that contains PDZ domain; it acts as an organizer of submembranous molecular complexes that control and coordinate polymerization of actin for the growth of membrane in stereocilia of inner and outer hair cells. Gene villin (9q32-q34), with 12 exons, codifies protein of the same name, with 465 amino acids and if mutant they are responsible for pre-lingual profound DFNB31.…”

Section: Molecular Genetics Of Non-syndromic Hearing Lossmentioning

confidence: 99%

See 2 more Smart Citations

Genética molecular da deficiência auditiva não-sindrômica

Piatto

Nascimento²,

Alexandrino³

et al. 2005

Rev. Bras. Otorrinolaringol.

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One in every 1,000 newborn suffers from congenital hearing impairment. More than 60% of the congenital cases are caused by genetic factors. In most cases, hearing loss is a multifactorial disorder caused by both genetic and environmental factors. Molecular genetics of deafness has experienced remarkable progress in the last decade. Genes responsible for hereditary hearing impairment are being mapped and cloned progressively. This review focuses on non-syndromic hearing loss, since the gene involved in this type of hearing loss have only recently begun to be identified.

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Pure monosomy and pure trisomy of 13q21.2–31.1 consequent to a familial insertional translocation: Exclusion of PCDH9 as the responsible gene for autosomal dominant auditory neuropathy (AUNA1)

Grati¹,

Lesperance

Toffol³

et al. 2009

American J of Med Genetics Pt A

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Insertional translocations (IT) are rare structural rearrangements. Offspring of IT balanced carriers are at high risk to have either pure partial trisomy or monosomy for the inserted segment as manifested by "pure" phenotypes. We describe an IT between chromosomes 3 and 13 segregating in a three-generation pedigree. Short tandem repeat (STR) segregation analysis and array-comparative genomic hybridization were used to define the IT as a 25.1 Mb segment spanning 13q21.2-q31.1. The phenotype of pure monosomy included deafness, duodenal stenosis, developmental and growth delay, vertebral anomalies, and facial dysmorphisms; the trisomy was manifested by only minor dysmorphisms. As the AUNA1 deafness locus on 13q14-21 overlaps the IT in the PCDH9 (protocadherin-9) gene region, PCDH9 was investigated as a candidate gene for deafness in both families. Genotyping of STRs and single nucleotide polymorphisms defined the AUNA1 breakpoint as 35 kb 5' to PCDH9, with a 2.4 Mb area of overlap with the IT. DNA sequencing of coding regions in the AUNA1 family and in the retained homologue chromosome in the monosomic patient revealed no mutations. We conclude that AUNA1 deafness does not share a common etiology with deafness associated with monosomy 13q21.2-q31.3; deafness may result from monosomy of PCHD9 or another gene in the IT, as has been demonstrated in contiguous gene deletion syndromes. Precise characterization of the breakpoints of the translocated region is useful to identify which genes may be contributing to the phenotype, either through haploinsufficiency or extra dosage effects, in order to define genotype-phenotype correlations.

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The molecular genetics of Usher syndrome

Cited by 140 publications

References 102 publications

The unconventional myosin-VIIa associates with lysosomes

The unconventional myosin-VIIa associates with lysosomes

Genética molecular da deficiência auditiva não-sindrômica

Pure monosomy and pure trisomy of 13q21.2–31.1 consequent to a familial insertional translocation: Exclusion of PCDH9 as the responsible gene for autosomal dominant auditory neuropathy (AUNA1)

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