Usher's Syndrome Type IC: Clinical Studies and Fine-Mapping the Disease Locus

Marietta, Jacquie; Walters, Katherine S.; Burgess, Rachel; Ni, Li; Fukushima, Kunihiro; Moore, Kenneth C.; Hejtmancik, J. F.; Smith, Richard J.H.

doi:10.1177/000348949710600206

Cited by 18 publications

(19 citation statements)

References 25 publications

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“…Our refinement of the critical region to between D11S902 and D11S1890 now excludes these two loci as the diseaseassociated gene (Figs. 1B and 2), consistent with failure to detect mutations in the KCNC1 gene in USH1C patients (Marietta et al 1997).…”

Section: Discussionsupporting

confidence: 65%

Contig Maps and Genomic Sequencing Identify Candidate Genes in the Usher 1C Locus

Higgins

Day²,

Smilinich³

et al. 1998

Genome Res.

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Usher syndrome 1C (USH1C) is a congenital condition manifesting profound hearing loss, the absence of vestibular function, and eventual retinal degeneration. The USH1C locus has been mapped genetically to a 2- to 3-cM interval in 11p14–15.1 between D11S899 andD11S861. In an effort to identify the USH1C disease gene we have isolated the region between these markers in yeast artificial chromosomes (YACs) using a combination of STS content mapping andAlu–PCR hybridization. The YAC contig is ∼3.5 Mb and has located several other loci within this interval, resulting in the orderCEN-LDHA-SAA1-TPH-D11S1310-(D11S1888/KCNC1)-MYOD1-D11S902D11S921-D11S1890-TEL.Subsequent haplotyping and homozygosity analysis refined the location of the disease gene to a 400-kb interval between D11S902 andD11S1890 with all affected individuals being homozygous for the internal marker D11S921. To facilitate gene identification, the critical region has been converted into P1 artificial chromosome (PAC) clones using sequence-tagged sites (STSs) mapped to the YAC contig, Alu–PCR products generated from the YACs, and PAC end probes. A contig of >50 PAC clones has been assembled between D11S1310 and D11S1890, confirming the order of markers used in haplotyping. Three PAC clones representing nearly two-thirds of the USH1C critical region have been sequenced. PowerBLAST analysis identified six clusters of expressed sequence tags (ESTs), two known genes (BIR,SUR1) mapped previously to this region, and a previously characterized but unmapped gene NEFA(DNA binding/EF hand/acidic amino-acid-rich). GRAIL analysis identified 11 CpG islands and 73 exons of excellent quality. These data allowed the construction of a transcription map for the USH1C critical region, consisting of three known genes and six or more novel transcripts. Based on their map location, these loci represent candidate disease loci for USH1C. The NEFA gene was assessed as the USH1C locus by the sequencing of an amplified NEFA cDNA from an USH1C patient; however, no mutations were detected.[The sequence data described in this paper have been submitted to GenBank under accession numbersAC000406–AC000407.]

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Section: Discussionsupporting

confidence: 65%

Contig Maps and Genomic Sequencing Identify Candidate Genes in the Usher 1C Locus

Higgins

Day²,

Smilinich³

et al. 1998

Genome Res.

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“…comm.) were initially screened with six microsatellite markers, DllS861, DllS419, DllS902, DllS921, DllS1310 and DllS899, located within or flanking the proximal or distal boundaries of the USH1C and HI critical regions (Ayyagari et al 1995;Glaser et al 1995;Marietta et al 1996). A total of 47 YAC clones were identified as positive for at least one of the six STSs used for screening.…”

Section: Isolation Of Yac Clonesmentioning

confidence: 99%

“…However, no YAC sequences homologous to the myosin VIIA gene were detected (data not shown). Additional candidate genes in the USHIC critical region are those encoding the potassium channel protein KCNC1 and myogenic factor 3 (MYOD1), although Marietta et al (1996) failed to detect mutations by single-strand conformation polymorphism (SSCP) analysis of the KCNC1 gene in USH 1C-affected individuals.…”

Section: Genome Research @ 509mentioning

confidence: 99%

“…Initially the USHIC locus was mapped by genetic linkage analyses in the French-Acadian population to a --3 cM region flanked by D11S861 and D11S899 (Ayyagari et al 1994;Keats et al 1994). Recently, the location for USH1C was refined to the interval between DllS902 and DllS1888 (Ayyagari et al 1995;Marietta et al 1996). Familial HI is characterized by excessive insulin secretion in the presence of severe hypoglycemia and occurs predominantly in neonates.…”

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confidence: 99%

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Construction of a YAC contig encompassing the Usher syndrome type 1C and familial hyperinsulinism loci on chromosome 11p14-15.1.

Ayyagari¹,

Nestorowicz²,

Li³

et al. 1996

Genome Res.

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The Usher syndrome type IC {USHIC} and familial hyperinsulinism [HI) loci have been assigned to chromosome Ilpl4-15.1, within the interval DIIS419-DI1SI310. We have constructed a yeast artificial chromosome {YAC} contig, extending from D11S926 to DIIS899, which encompasses the critical regions for both USHIC and HI and spans an estimated genetic distance of ---4 cM. A minimal set of six YAC clones constitute the contig, with another 22 YACs confirming the order of sequence-tagged sites [STSs) and position of YACs on the contig. A total of 40 STSs, including 10 new STSs generated from YAC insert-end sequences and inter-A/u PCR products, were used to order the clones within the contig. This physical map provides a resource for identification of gene transcripts associated with USHIC, HI, and other genetic disorders that map to the DllS?26-DIIS899 interval.

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“…Narrow blood vessels, pale optic disc and balance problems are also observed in individuals affected with USH [85]. Beside these, symptoms like structural anomalies of nasal cilia [86,87], olfactory loss is also found in the USH patients [88]. The characteristic features of X-linked Alport syndrome are ocular problems, hematuria, glomerulonephritis, renal failure and sensorineural deafness.…”

Section: Clinical Features Of Deafnessmentioning

confidence: 99%