Implications of intragenic marker homozygosity and haplotype sharing in a rare autosomal recessive disorder: the example of the collagen type XVII (COL17A1) locus in generalised atrophic benign epidermolysis bullosa |
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Authors: | H Scheffer Rein P Stulp Edwin Verlind M van der Meulen Leena Bruckner-Tuderman Tobias Gedde-Dahl Jr G J te Meerman Arnoud Sonnenberg Charles H C M Buys Marcel F Jonkman |
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Institution: | (1) Department of Medical Genetics, University of Groningen, Antonius Deusinglaan 4, NL-9713 AW Groningen, The Netherlands Tel.: +31-50-3632925; Fax: +31-50-3632947; e-mail: h.scheffer@med.rug.nl, NL;(2) Department of Dermatology, University of Münster, Münster, Germany, DE;(3) Department of Dermatology and Institute of Forensic Medicine, National Hospital, Oslo, Norway, NO;(4) Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands, NL;(5) Department of Dermatology, University Hospital Groningen, Groningen, The Netherlands, NL |
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Abstract: | Generalised atrophic benign epidermolysis bullosa (GABEB) is a form of junctional epidermolysis bullosa with a recessive
mode of inheritance. The gene considered likely to be involved in this disease is COL17A1, since in the majority of GABEB
patients the product of that gene, the 180-kD bullous pemphigoid antigen (BP180), is undetectable in skin. We have identified
an intragenic COL17A1 microsatellite marker for which 83% of randomly selected control individuals are heterozygous. We observed
homozygosity for different alleles of this marker in five out of six collagen type XVII-negative GABEB patients of different
European descent. Five of the six COL17A1 alleles of three patients originating from the eastern part of The Netherlands were
identical, as were the haplotypes including flanking markers. The 2342delG mutation was identified in all these five alleles.
This confirms the expectation that due to genetic drift and hidden inbreeding for an autosomal recessive disorder with low
gene frequency, such as collagen type XVII-negative GABEB, most disease alleles from a restricted geographical area will be
“identical by descent”. Our results demonstrate that involvement of a candidate gene can be confirmed by looking for identity
by descent of highly informative intragenic markers.
Received: 25 October 1996 / Accepted: 6 March 1997 |
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