Refined Mapping of the Usher Syndrome Type III Locus on Chromosome 3, Exclusion of Candidate Genes, and Identification of the Putative Mouse Homologous Region

Joensuu, Tarja; Blanco, Gonzalo; Pakarinen, Leenamaija; Sistonen, Pertti; Kääriäinen, Helena; Brown, Steve; Chapelle, Albert de la; Sankila, Eeva‐Marja

doi:10.1006/geno.1996.0626

Cited by 32 publications

(31 citation statements)

References 5 publications

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“…On the other hand, none of our affected individuals were diagnosed clinically as USIII, while other populations showed values ranging from 1 to 40% [3, 38, 39]. The frequency of this Usher type is low (1% of all cases) [2], but it is striking that the proportion of USIII is estimated at 40% of all the US cases in the Finnish population [38, 39]. A founder effect has been suggested to explain the high incidence of US type III in this country [39], and this reinforces the idea that USIII is a clinical entity.…”

Section: Discussionmentioning

confidence: 99%

“…This Usher variety is easier to detect among the blind population because the hearing impairment is not so severe as to require attendance at schools for the deaf. On the other hand, none of our affected individuals were diagnosed clinically as USIII, while other populations showed values ranging from 1 to 40% [3, 38, 39]. The frequency of this Usher type is low (1% of all cases) [2], but it is striking that the proportion of USIII is estimated at 40% of all the US cases in the Finnish population [38, 39].…”

Section: Discussionmentioning

confidence: 99%

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Epidemiology of Usher Syndrome in Valencia and Spain

Espinós

Millán²,

Beneyto³

et al. 1998

Public Health Genomics

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Objective: To obtain epidemiological data on the prevalence of the different types of Usher syndrome (US) in Spain, since these data were missing; to estimate the proportion of sporadic cases among simplex families, and calculate the prevalence of the Usher syndrome in a homogeneous population from Eastern Spain (3,875,234 inhabitants) that is representative of the Spanish population. Methods: Otological, ophthalmological and genetic studies were performed in 89 US patients from 46 families and subjected to statistical and segregation analysis. Results: 41.6% of them suffered US type I, 46.1% type II, and in 12.3% the classification remains unclear. The estimated prevalence for the Province of Valencia was 4.2/100,000. There was a notable excess of male-only affected multiplex sibships in our sample that could be attributable to an X-linked inheritance. Conclusions: The number of families with USI type was similar to that of families with USII type. The estimated prevalence for the Province of Valencia is in agreement with other reports in which the estimate for the prevalence of US ranges from 1.8 to 6.2/100,000.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Epidemiology of Usher Syndrome in Valencia and Spain

Espinós

Millán²,

Beneyto³

et al. 1998

Public Health Genomics

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“…Clinical and genealogical data on the Finnish and Italian families with USH3 that are studied here also have been described elsewhere Sankila et al 1995;Joensuu et al 1996Joensuu et al , 2000Gasparini et al 1998). Control DNA samples from 100 anonymous blood donors from eastern Finland (where there is a high prevalence of USH3) and from 100 donors from western and southern Finland (where there is a low prevalence of USH3) were provided by the Finnish Red Cross Blood Transfusion Service.…”

Section: Families With Ush3 and Controlsmentioning

confidence: 99%

“…Amplification of genomic DNA was performed as described elsewhere (Joensuu et al 1996). For RT-PCR, either 200 ng of lymphoblast poly(A) RNA or 1 mg of total RNA was primed by random hexamers and was reverse transcribed for the first-strand synthesis of cDNA.…”

Section: Pcr and Rt-pcrmentioning

confidence: 99%

“…Significant linkage disequilibrium between USH3 and the linked markers suggested enrichment of a founder mutation in Finland and allowed us to refine the localization of USH3 to a 250-kb genomic interval between markers 107G19CA7 and D3S3625 (Joensuu et al 1996(Joensuu et al , 2000. Haplotype analysis indicated 107G19CA7 to be the proximal historic recombination breakpoint, and a recombination in one family with USH3 placed the USH3 gene proximal to D3S3625.…”

Section: Introductionmentioning

confidence: 95%

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Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3

2001

Am. J Hum. Genet.

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Usher syndrome type 3 (USH3) is an autosomal recessive disorder characterized by progressive hearing loss, severe retinal degeneration, and variably present vestibular dysfunction, assigned to 3q21-q25. Here, we report on the positional cloning of the USH3 gene. By haplotype and linkage-disequilibrium analyses in Finnish carriers of a putative founder mutation, the critical region was narrowed to 250 kb, of which we sequenced, assembled, and annotated 207 kb. Two novel genes-NOPAR and UCRP-and one previously identified gene-H963-were excluded as USH3, on the basis of mutational analysis. USH3, the candidate gene that we identified, encodes a 120-amino-acid protein. Fifty-two Finnish patients were homozygous for a termination mutation, Y100X; patients in two Finnish families were compound heterozygous for Y100X and for a missense mutation, M44K, whereas patients in an Italian family were homozygous for a 3-bp deletion leading to an amino acid deletion and substitution. USH3 has two predicted transmembrane domains, and it shows no homology to known genes. As revealed by northern blotting and reverse-transcriptase PCR, it is expressed in many tissues, including the retina.

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The Usher syndromes

Keats

Corey²

1999

Am. J. Med. Genet.

138

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Mutations in the gene (MYO7A) encoding myosin-VIIa, a member of the large superfamily of myosin motor proteins that move on cytoplasmic actin filaments, and in the USH2A gene, which encodes a novel protein resembling an extracellular matrix protein or a cell adhesion molecule, both cause Usher syndrome (USH), a clinically heterogeneous autosomal recessive disorder comprising hearing and visual impairment. Patients with USH1 have severe to profound congenital hearing impairment, vestibular dysfunction, and retinal degeneration beginning in childhood, while those with USH2 have moderate to severe hearing impairment, normal vestibular function, and later onset of retinal degeneration. USH3 is characterized by progressive hearing loss and variable age of onset of retinal degeneration. The phenotype resulting from MYO7A and USH2A mutations is variable. While most MYO7A mutations cause USH1, some cause nonsyndromic hearing impairment, and one USH3 phenotype has been described. USH2A mutations cause atypical USH as well as USH2. MYO7A is on chromosome region 11q13 and USH2A is on 1q41. Seven other USH genes have been mapped but have not yet been identified. USH1A, USH1C, USH1D, USH1E, and USH1F have been assigned to chromosome bands 14q32, 11p15.1, 10q, 21q21, and 10, respectively, while USH2B is on 5q, and USH3 is at 3q21-q25. Myosin VIIa mutations also result in the shaker-1 (sh1) mouse, providing a model for functional studies. One possibility is that myosin-VIIa is required for linking stereocilia in the sensory hair bundle; another is that it may be needed for membrane trafficking. The ongoing studies of myosin-VIIa, the USH2A protein, and the yet to be identified proteins encoded by the other USH genes will advance understanding of the Usher syndromes and contribute to the development of effective therapies. Am. J. Med. Genet. (Semin. Med. Genet.) 89:158-166, 1999.

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Refined Mapping of the Usher Syndrome Type III Locus on Chromosome 3, Exclusion of Candidate Genes, and Identification of the Putative Mouse Homologous Region

Cited by 32 publications

References 5 publications

Epidemiology of Usher Syndrome in Valencia and Spain

Epidemiology of Usher Syndrome in Valencia and Spain

Mutations in a Novel Gene with Transmembrane Domains Underlie Usher Syndrome Type 3

The Usher syndromes

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