A novel locus for Usher syndrome type I, USH1G, maps to chromosome 17q24–25

Mustapha, Mirna; Chouery, Éliane; Torchard-Pagnez, Delphine; Nouaille, Sylvie; Khrais, Awni; Sayegh, Fouad N.; Mégarbané, André; Loiselet, Jacques; Lathrop, Mark; Petit, Christine; Weil, Dominique

doi:10.1007/s00439-002-0690-x

Cited by 59 publications

(30 citation statements)

References 8 publications

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“…Mutations in any one of seven different genes can effect the same type of deafness-blindness that is characterized by Usher syndrome type 1 (USH1) (Petit, 2001;Mustapha et al, 2002). Thus, there are seven subtypes of USH1, USH1A through USH1G.…”

Section: Introductionmentioning

confidence: 99%

Role of myosin VIIa and Rab27a in the motility and localization of RPE melanosomes

Gibbs

Azarian

Lillo

et al. 2004

Journal of Cell Science

135

159

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Myosin VIIa functions in the outer retina, and loss of this function causes human blindness in Usher syndrome type 1B (USH1B). In mice with mutant Myo7a, melanosomes in the retinal pigmented epithelium (RPE) are distributed abnormally. In this investigation we detected many proteins in RPE cells that could potentially participate in melanosome transport, but of those tested, only myosin VIIa and Rab27a were found to be required for normal distribution. Two other expressed proteins, melanophilin and myosin Va, both of which are required for normal melanosome distribution in melanocytes, were not required in RPE, despite the association of myosin Va with the RPE melanosome fraction. Both myosin VIIa and myosin Va were immunodetected broadly in sections of the RPE, overlapping with a region of apical filamentous actin. Some 70-80% of the myosin VIIa in RPE cells was detected on melanosome membranes by both subcellular fractionation of RPE cells and quantitative immunoelectron microscopy, consistent with a role for myosin VIIa in melanosome motility. Time-lapse microscopy of melanosomes in primary cultures of mouse RPE cells demonstrated that the melanosomes move in a saltatory manner, interrupting slow movements with short bursts of rapid movement (>1 μm/second). In RPE cells from Myo7a-null mice, both the slow and rapid movements still occurred, except that more melanosomes underwent rapid movements, and each movement extended approximately five times longer (and further). Hence, our studies demonstrate the presence of many potential effectors of melanosome motility and localization in the RPE, with a specific requirement for Rab27a and myosin VIIa, which function by transporting and constraining melanosomes within a region of filamentous actin. The presence of two distinct melanosome velocities in both control and Myo7a-null RPE cells suggests the involvement of at least two motors other than myosin VIIa in melanosome motility, most probably, a microtubule motor and myosin Va.

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Section: Introductionmentioning

confidence: 99%

Role of myosin VIIa and Rab27a in the motility and localization of RPE melanosomes

Gibbs

Azarian

Lillo

et al. 2004

Journal of Cell Science

135

159

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“…The USH1G locus was mapped to chromosome 17q in a consanguineous Jordanian family [Mustapha et al, 2002] and the causative gene was quickly identified as SANS, which is mutated in the Jackson shaker mouse Weil et al, 2003]. As might be anticipated, these mice have disorganized hair bundles.…”

Section: Ush1gmentioning

confidence: 98%

Genetic heterogeneity in Usher syndrome

Keats

Savas

2004

American J of Med Genetics Pt A

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Mutations in seven different genes have been associated with Usher syndrome, and an additional four loci have been mapped. The identified genes encode myosin VIIa, harmonin (a PDZ-domain protein), cadherin 23, protocadherin 15, sans (a scaffold-like protein), usherin and clarin. Three clinical types of Usher syndrome have been described: USH1 patients have severe to profound congenital hearing loss, vestibular dysfunction, and retinal degeneration beginning in childhood, those with USH2 have moderate to severe congenital hearing loss, normal vestibular function, and later onset of retinitis pigmentosa, and USH3 patients have progressive hearing loss, which distinguishes them from the other two types. The shaker-1, waltzer, Ames waltzer, and Jackson shaker mice provide murine models for four of the genetic forms of Usher syndrome. Ongoing studies are enabling early diagnosis of Usher syndrome in children who present with hearing loss, thus providing time to prepare for the onset of visual loss.

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“…Genes for seven USH1 loci have been mapped (4,6) and five have been cloned (7)(8)(9)(10)(11). Myosin VIIA (MYO7A) underlies USH1B, as well as NSHL DFNA11 and what was originally described as DFNB2, but is now considered to be atypical USH1 (10,(12)(13)(14)(15).…”

mentioning

confidence: 99%