Defective myosin VIIA gene responsible for Usher syndrome type IB (original) (raw)

• Letter
• Published: 02 March 1995
• Stéphane Blanchard1,
• Josseline Kaplan2,
• Parry Guilford1,
• Fernando Gibson3,
• James Walsh3,
• Philomena Mburu3,
• Anabel Varela3,
• Jacqueline Levilliers1,
• Michael D. Weston4,
• Phillip M. Kelley4,
• William J. Kimberling4,
• Mariette Wagenaar5,
• Fabienne Levi-Acobas1,
• Dominique Larget-Piet2,
• Arnold Munnich1,
• Karen P. Steel6,
• Steve D. M. Brown3 &
• …
• Christine Petit6

Nature volume 374, pages 60–61 (1995)Cite this article

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Abstract

USHER syndrome represents the association of a hearing impairment with retinitis pigmentosa1 and is the most frequent cause of deaf–blindness in humans. It is inherited as an autosomal recessive trait which is clinically and genetically heterogeneous2,3. Some patients show abnormal organization of microtubules in the axoneme of their photoreceptors cells (connecting cilium)4–6, nasal ciliar cells7 and sperm cells5, as well as widespread degeneration of the organ of Corti8. 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 USH19–11,USH1B maps to 11q13.5 (ref. 10) and accounts for about 75% of USH1 patients2,3. The mouse deafness shaker-1 (shl) mutation has been localized to the homologous murine region12,13. 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 homo-logue 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 USH IB 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.

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Authors and Affiliations

1. Unité de Génétique Moléculaire Humaine (URA CNRS 1968), Institut Pasteur, 25 rue du Docteur Roux, 75724, Paris, Cedex 15, France
   Dominique Well, Stéphane Blanchard, Parry Guilford, Jacqueline Levilliers, Fabienne Levi-Acobas & Arnold Munnich
2. Unité de Recherches sur les Handicaps Génétiques de I'Enfant (INSERM U393), Hôpital des Enfants Malades, 149 rue de Sèvres, 75743, Paris, Cedex 15, France
   Josseline Kaplan & Dominique Larget-Piet
3. Department of Biochemistry and Molecular Genetics, St Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, W2 1PG, UK
   Fernando Gibson, James Walsh, Philomena Mburu, Anabel Varela & Steve D. M. Brown
4. Department of Pathology, Boys Town National Research Hospital, Omaha, Nebraska, 68131, USA
   Michael D. Weston, Phillip M. Kelley & William J. Kimberling
5. Katholieke Universiteit Nimegen, Sint Radboudziekiekenhuis, 6500 HB, Nijmegen, The Netherlands
   Mariette Wagenaar
6. MRC Institute of Hearing Research, University Park, Nottingham, NG7 2RD, UK
   Karen P. Steel & Christine Petit

Authors

1. Dominique Well
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2. Stéphane Blanchard
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3. Josseline Kaplan
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4. Parry Guilford
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5. Fernando Gibson
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6. James Walsh
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7. Philomena Mburu
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8. Anabel Varela
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9. Jacqueline Levilliers
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10. Michael D. Weston
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11. Phillip M. Kelley
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12. William J. Kimberling
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13. Mariette Wagenaar
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14. Fabienne Levi-Acobas
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15. Dominique Larget-Piet
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16. Arnold Munnich
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17. Karen P. Steel
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18. Steve D. M. Brown
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19. Christine Petit
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Well, D., Blanchard, S., Kaplan, J. et al. Defective myosin VIIA gene responsible for Usher syndrome type IB.Nature 374, 60–61 (1995). https://doi.org/10.1038/374060a0

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• Received: 21 November 1994
• Accepted: 20 January 1995
• Issue Date: 02 March 1995
• DOI: https://doi.org/10.1038/374060a0

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