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| DEFECTIVE MYOSIN VIIA GENE RESPONSIBLE FOR USHER SYNDROME TYPE 1B |
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| Author(s): WELL D, BLANCHARD S, KAPLAN J, GUILFORD P, GIBSON F, WALSH J, MBURU P, VARELA A, LEVILLERS J, WESTON MD, KELLEY PM, KIMBERLING WJ, WAGENAAR M, LEVIACOBAS F, LARGETPIET D, MUNNICH A, STEEL KP, BROWN SDM, PETIT C |
| Source: NATURE Volume: 374 Issue: 6517 Pages: 60-61 Published: MAR 2 1995 |
| Times Cited: 96 References: 31 |
| Abstract: USHER syndrome represents the association of a hearing impairment with retinitis pigmentosa(1) and is the most frequent cause of deaf-blindness in humans. it is inherited as an autosomal recessive trait which is clinically and genetically heterogeneous(2,3). Some patients show abnormal organization of microtubules in the axoneme of their photoreceptors cells (connecting cilium)(4-6), nasal ciliar cells(7) and sperm cells(5), as well as widespread degeneration of the organ of Corti(8). Usher syndrome type 1 (USH1) is characterized by a profound congenital sensorineural hearing loss, constant vestibular dysfunction and prepubertal onset of retinitis pigmentosa. Of three different genes responsible for USH1(9-11) USH1B maps to 11q13.5 (ref. 10) and accounts for about 75% of USH1 patients(2,3). The mouse deafness shaker-1 (sh1) mutation has been localized to the homologous murine region(12,13). Taking into account the cytoskeletal abnormalities in USH patients, the identification of a gene encoding an unconventional myosin as a candidate for shaker-1 (ref. 14) led us to consider the human homologue as a good candidate for the gene that is defective in USH1B. Here we present evidence that a gene encoding myosin VIIA is responsible for USH1B. Two different premature stop codons, a six-base-pair deletion and two different missense mutations were detected in five unrelated families. In one of these families, the mutations were identified in both alleles. These mutations, which are located at the amino-terminal end of the motor domain of the protein, are likely to result in the absence of a functional protein. Thus USH1B appears as a primary cytoskeletal protein defect. These results implicate the genes encoding other unconventional myosins and their interacting proteins as candidates for other genetic forms of Usher syndrome. |
| Document Type: Article |
| Language: English |
Addresses:
1. INST PASTEUR, CNRS, UNITE GENET MOLEC HUMAINE 1968, F-75724 PARIS 15, FRANCE
2. HOP NECKER ENFANTS MALAD, INSERM, U393, UNITE RECH HANDICAPS GENET ENFANT, F-75743 PARIS 15, FRANCE
3. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED, ST MARYS HOSP, SCH MED, DEPT BIOCHEM & MOLEC GENET, LONDON W2 1PG, ENGLAND
4. BOYS TOWN NATL RES HOSP, DEPT PATHOL, OMAHA, NE 68131 USA
5. CATHOLIC UNIV NIJMEGEN, ST RADBOUD HOSP, 6500 HB NIJMEGEN, NETHERLANDS
6. MRC, INST HEARING RES, NOTTINGHAM NG7 2RD, ENGLAND |
| Publisher: MACMILLAN MAGAZINES LTD, 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: QK079 |
| ISSN: 0028-0836 |
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