Scheffer H, Stulp R P, Verlind E, van der Meulen M, Bruckner-Tuderman L, Gedde-Dahl T, te Meerman G J, Sonnenberg A, Buys C H, Jonkman M F
Department of Medical Genetics, University of Groningen, The Netherlands.
Hum Genet. 1997 Aug;100(2):230-5. doi: 10.1007/s004390050496.
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.
泛发性萎缩性良性大疱性表皮松解症（GABEB）是交界性大疱性表皮松解症的一种形式，呈隐性遗传模式。被认为可能与该疾病相关的基因是COL17A1，因为在大多数GABEB患者的皮肤中无法检测到该基因的产物，即180-kD大疱性类天疱疮抗原（BP180）。我们鉴定出一个COL17A1基因内微卫星标记，在随机选择的对照个体中，83%为杂合子。在6名不同欧洲血统的XVII型胶原阴性GABEB患者中，有5名患者该标记的不同等位基因出现纯合性。来自荷兰东部的3名患者的6个COL17A1等位基因中有5个相同，包括侧翼标记的单倍型也是如此。在所有这5个等位基因中均鉴定出2342delG突变。这证实了这样的预期，即对于像XVII型胶原阴性GABEB这种基因频率较低的常染色体隐性疾病，由于遗传漂变和隐藏的近亲繁殖，来自有限地理区域的大多数疾病等位基因将“同源相同”。我们的结果表明，通过寻找高信息性基因内标记的同源相同性，可以证实候选基因的参与情况。
