Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family
This study aimed to identify genetic mechanisms underlying severe retinal degeneration in one large family from northern Sweden, members of which presented with early-onset autosomal recessive retinitis pigmentosa and juvenile macular dystrophy. The clinical records of affected family members were a...
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Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798833 http://www.ncbi.nlm.nih.gov/pubmed/23443024 https://doi.org/10.1038/ejhg.2013.23 |
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ftpubmed:oai:pubmedcentral.nih.gov:3798833 2023-05-15T17:44:51+02:00 Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family Jonsson, Frida Burstedt, Marie S Sandgren, Ola Norberg, Anna Golovleva, Irina 2013-11 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798833 http://www.ncbi.nlm.nih.gov/pubmed/23443024 https://doi.org/10.1038/ejhg.2013.23 en eng Nature Publishing Group http://www.ncbi.nlm.nih.gov/pmc/articles/PMC http://www.ncbi.nlm.nih.gov/pubmed/23443024 http://dx.doi.org/10.1038/ejhg.2013.23 Copyright © 2013 Macmillan Publishers Limited Article Text 2013 ftpubmed https://doi.org/10.1038/ejhg.2013.23 2014-11-02T00:59:15Z This study aimed to identify genetic mechanisms underlying severe retinal degeneration in one large family from northern Sweden, members of which presented with early-onset autosomal recessive retinitis pigmentosa and juvenile macular dystrophy. The clinical records of affected family members were analysed retrospectively and ophthalmological and electrophysiological examinations were performed in selected cases. Mutation screening was initially performed with microarrays, interrogating known mutations in the genes associated with recessive retinitis pigmentosa, Leber congenital amaurosis and Stargardt disease. Searching for homozygous regions with putative causative disease genes was done by high-density SNP-array genotyping, followed by segregation analysis of the family members. Two distinct phenotypes of retinal dystrophy, Leber congenital amaurosis and Stargardt disease were present in the family. In the family, four patients with Leber congenital amaurosis were homozygous for a novel c.2557C>T (p.Q853X) mutation in the CRB1 gene, while of two cases with Stargardt disease, one was homozygous for c.5461-10T>C in the ABCA4 gene and another was carrier of the same mutation and a novel ABCA4 mutation c.4773+3A>G. Sequence analysis of the entire ABCA4 gene in patients with Stargardt disease revealed complex alleles with additional sequence variants, which were evaluated by bioinformatics tools. In conclusion, presence of different genetic mechanisms resulting in variable phenotype within the family is not rare and can challenge molecular geneticists, ophthalmologists and genetic counsellors. Text Northern Sweden PubMed Central (PMC) European Journal of Human Genetics 21 11 1266 1271 |
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Article Jonsson, Frida Burstedt, Marie S Sandgren, Ola Norberg, Anna Golovleva, Irina Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family |
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Article |
description |
This study aimed to identify genetic mechanisms underlying severe retinal degeneration in one large family from northern Sweden, members of which presented with early-onset autosomal recessive retinitis pigmentosa and juvenile macular dystrophy. The clinical records of affected family members were analysed retrospectively and ophthalmological and electrophysiological examinations were performed in selected cases. Mutation screening was initially performed with microarrays, interrogating known mutations in the genes associated with recessive retinitis pigmentosa, Leber congenital amaurosis and Stargardt disease. Searching for homozygous regions with putative causative disease genes was done by high-density SNP-array genotyping, followed by segregation analysis of the family members. Two distinct phenotypes of retinal dystrophy, Leber congenital amaurosis and Stargardt disease were present in the family. In the family, four patients with Leber congenital amaurosis were homozygous for a novel c.2557C>T (p.Q853X) mutation in the CRB1 gene, while of two cases with Stargardt disease, one was homozygous for c.5461-10T>C in the ABCA4 gene and another was carrier of the same mutation and a novel ABCA4 mutation c.4773+3A>G. Sequence analysis of the entire ABCA4 gene in patients with Stargardt disease revealed complex alleles with additional sequence variants, which were evaluated by bioinformatics tools. In conclusion, presence of different genetic mechanisms resulting in variable phenotype within the family is not rare and can challenge molecular geneticists, ophthalmologists and genetic counsellors. |
format |
Text |
author |
Jonsson, Frida Burstedt, Marie S Sandgren, Ola Norberg, Anna Golovleva, Irina |
author_facet |
Jonsson, Frida Burstedt, Marie S Sandgren, Ola Norberg, Anna Golovleva, Irina |
author_sort |
Jonsson, Frida |
title |
Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family |
title_short |
Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family |
title_full |
Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family |
title_fullStr |
Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family |
title_full_unstemmed |
Novel mutations in CRB1 and ABCA4 genes cause Leber congenital amaurosis and Stargardt disease in a Swedish family |
title_sort |
novel mutations in crb1 and abca4 genes cause leber congenital amaurosis and stargardt disease in a swedish family |
publisher |
Nature Publishing Group |
publishDate |
2013 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798833 http://www.ncbi.nlm.nih.gov/pubmed/23443024 https://doi.org/10.1038/ejhg.2013.23 |
genre |
Northern Sweden |
genre_facet |
Northern Sweden |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC http://www.ncbi.nlm.nih.gov/pubmed/23443024 http://dx.doi.org/10.1038/ejhg.2013.23 |
op_rights |
Copyright © 2013 Macmillan Publishers Limited |
op_doi |
https://doi.org/10.1038/ejhg.2013.23 |
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European Journal of Human Genetics |
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21 |
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11 |
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1266 |
op_container_end_page |
1271 |
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1766147147254726656 |