Department of Dermatology, Columbia University, New York, NY 10032, USA.
Dermatology. 2010;220(3):208-12. doi: 10.1159/000275673. Epub 2010 Mar 5.
Hypotrichosis with juvenile macular dystrophy (HJMD; OMIM 601553) is a rare autosomal recessive disorder characterized by hypotrichosis with short scalp hair and progressive macular dystrophy leading to blindness between the second and the fourth decades of life. HJMD is caused by mutations in the P-cadherin gene (CDH3), a member of the family of classical cadherins.
We analyzed the DNA from members of 2 consanguineous Pakistani families with HJMD for mutations in the P-cadherin gene through direct sequencing.
We identified 2 splice site mutations in the P-cadherin gene in these families. One was a novel mutation, Ivs12-2A-->G and the other a recurrent mutation, Ivs10-1G-->T. A screening assay for the novel mutation ruled out the possibility of a polymorphism. Using haplotype analysis, we determined that the mutation, Ivs10-1G-->T, is a founder mutation in the Pakistani population.
We identified 2 splice site mutations in the CDH3 gene leading to HJMD, further enriching our understanding of HJMD versus ectodermal dysplasia, ectrodactyly and macular dystrophy syndrome.
少年性毛发稀少伴黄斑营养不良（HJMD；OMIM 601553）是一种罕见的常染色体隐性遗传疾病，其特征为毛发稀少，头皮毛发短，进行性黄斑营养不良导致 20 至 40 岁之间失明。HJMD 是由 P-钙黏蛋白基因（CDH3）突变引起的，该基因是经典钙黏蛋白家族的成员之一。
我们通过直接测序，分析了 2 个有血缘关系的巴基斯坦 HJMD 家族成员的 DNA 中 P-钙黏蛋白基因的突变。
我们在这两个家族中发现了 P-钙黏蛋白基因中的 2 个剪接位点突变。一个是新的突变，Ivs12-2A-->G，另一个是复发的突变，Ivs10-1G-->T。对新突变的筛选检测排除了多态性的可能性。通过单倍型分析，我们确定 Ivs10-1G-->T 突变是巴基斯坦人群中的一个创始突变。
我们鉴定了导致 HJMD 的 CDH3 基因中的 2 个剪接位点突变，进一步丰富了我们对 HJMD 与外胚层发育不良、并指（趾）畸形和黄斑营养不良综合征的认识。
