Viewing options:

Abstract
Full text
PDF (966KB)
Additional files

Associated material:

PubMed record

Related literature:

Articles citing this article
on Google Scholar
on ISI Web of Science
on PubMed Central
Other articles by authors
on Google Scholar

Ebermann I
Lopez I
Bitner-Glindzicz M
Brown C
Koenekoop RK
Bolz HJ

on PubMed

Ebermann I
Lopez I
Bitner-Glindzicz M
Brown C
Koenekoop RK
Bolz HJ
Related articles/pages
on Google

on Google Scholar

on PubMed

Tools:

Post to:

Research

Deafblindness in French Canadians from Quebec: a predominant founder mutation in the USH1C gene provides the first genetic link with the Acadian population

Inga Ebermann¹ , Irma Lopez² , Maria Bitner-Glindzicz³ , Carolyn Brown² , Robert Karel Koenekoop² and Hanno Jörn Bolz¹

¹Institute of Human Genetics, University Hospital of Cologne, Kerpener Str., 50931 Cologne, Germany

²McGill Ocular Genetics Laboratory, Montreal Children's Hospital Research Institute, Tupper, Montreal, PQ, Canada, H3H 1P3

³Unit of Clinical and Molecular Genetics, Institute of Child Health, University College London, Guilford St, London WC1N 1EH, UK

author email corresponding author email

Genome Biology 2007, 8:R47doi:10.1186/gb-2007-8-4-r47


Published:	3 April 2007

Subject areas: Genetics, Genome studies, Medicine, Physiology

Additional files

Additional data file 1:

USH1C genotypes identified in this study. (a) The family of an Acadian USH1 patient that has previously been shown to be homozygous for the Acadian founder mutation, c.216G>A [5], was available for haplotype analysis. USH1C haplotypes are represented by vertical colored bars (c.216G>A-associated haplotype in red). See Figure 1b and Figure 2 for detailed haplotypes. (b) Two brothers with homozygosity for c.216G>A, which was also found in patients 367, 1116, and 1172. (c) Compound heterozygosity for c.216G>A and c.238-239insC in two brothers. (d) Compound heterozygosity for c.216G>A and the novel nonsense mutation p.R155X (patient 475). (e) Compound heterozygosity for c.216G>A and a novel splice site mutation, c.496+1G>T, which affects the invariant donor splice site of exon 5 (patients 848 and 1115). (f) Compound heterozygosity for c.238-239insC and the novel 17 bp deletion 748_759+5del, which removes 12 exonic and five intronic base-pairs, including the donor splice site of exon 9 (patient 465).

Format: TIFF Size: 2.2MB Download file

Additional data file 2:

SNPs in bold are referred to in Figure 2. '∅' indicates absence of the 9VNTR(t,t) allele. European: haplotype associated with c.238-239insC in European patients as published by Zwaenepoel et al. [15]. 1-2: haplotype associated with c.238-239insC in our patients (compound heterozygosity for c.748_759+5del and c.216G>A, respectively). Common haplotypes in Quebec and European USH1 patients carrying the c.238-239insC mutation suggest that the mutation probably has recently been locally 'imported' by other ethnic communities after completion of settlement. Note different alleles for D11S1349 on the chromosome carrying c.238-239insC in patients 465 and 505, respectively. 3: haplotype associated with c.496+1G>T. 4 and 5: Haplotypes associated with novel mutations c.748_759+5del and p.R155X, respectively.

Format: TIFF Size: 691KB Download file

Additional data file 3:

Homozygosity for the CDH23 mutation IVS45-9G>A was found in patients 303 and 1235, while patient 860 was compound heterozygous for IVS45-9G>A and the novel nonsense mutation p.R736X. SNP alleles are given according to the genomic CDH23 sequence in 5'-3' orientation. The haplotype associated with IVS45-9G>A in Quebec patients matches with the CDH23 haplotype of two German families that we have investigated previously [19]. As in the case of c.238-239insC, this could be due to settlement of ethnic groups other than French Canadians. Note recombination event for marker D10S1759 in patient 1235. N.d. = not determined.

Format: DOC Size: 55KB Download file

This file can be viewed with: Microsoft Word Viewer

Additional data file 4:

The map illustrates the location of the places given in the table (cities associated with patients carrying c.216G>A in red). See also Figure 1a.

Format: TIFF Size: 1.2MB Download file

Additional data file 5:

Fragment length analysis is shown for microsatellite markers (GeneScan, Applied Biosystems), electropherograms for SNPs, and agarose gel electrophoresis for the VNTR in intron 5 of the USH1C gene.

Format: PDF Size: 3.9MB Download file

This file can be viewed with: Adobe Acrobat Reader

Additional data file 6:

All mutations that have been identified in USH1 patients that have been investigated in this study (electropherograms), and figures for genotyping of healthy French Canadian control individuals for these mutations (by direct sequencing, restriction enzyme digest, and fragment length analysis).

Format: PDF Size: 9.3MB Download file

This file can be viewed with: Adobe Acrobat Reader

Additional data file 7:

Results of mutation screening in patient 1881 in the genes MYO7A (USH1B) and USH1C (no mutations found).

Format: PDF Size: 8.6MB Download file

This file can be viewed with: Adobe Acrobat Reader

Additional data file 8:

Results of mutation screening in patient 1881 in the CDH23 gene (USH1D) (no mutations found).

Format: PDF Size: 8.3MB Download file

This file can be viewed with: Adobe Acrobat Reader

Additional data file 9:

Results of mutation screening in patient 1881 in the genes PCDH15 (USH1F), SANS (USH1G) and USH3A (no mutations found).

Format: PDF Size: 5.6MB Download file

This file can be viewed with: Adobe Acrobat Reader