Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Clin Genet. 2011 Mar;79(3):273-81. doi: 10.1111/j.1399-0004.2010.01455.x.
Hypotrichosis is a human hereditary hair loss disorder in which affected individuals show sparse to complete absence of hair on scalp and/or on different body parts. To date, at least eight isolated autosomal recessive and dominant forms of hypotrichosis loci have been mapped on different human chromosomes, and the corresponding genes have been identified. Detailed clinical and molecular studies were undertaken of the hereditary hypotrichosis observed in the two consanguineous families (A and B) presented here. Human genome scan, using >500 highly polymorphic microsatellite markers, identified equal evidence of linkage of the hypotrichosis phenotype on chromosomes 12q21.2-q22 and 16q21-q23.1 in both the families. The novel hypotrichosis locus on chromosome 12q21.2-q22 spans 16.3 cM (17.62 Mb), flanked by markers D12S326 and D12S101. At this locus, maximum multipoint logarithm of the odds ratio (LOD) scores of 3.68 and 3.31 were obtained in families A and B, respectively. The second hypotrichosis locus on chromosome 16q21-q23.1, identified in the two families, spans 5.58 cM (8.28 Mb) and is flanked by markers D16S3031 and D16S512. Maximum multipoint LOD scores of 3.17 and 3.31 were obtained with markers mapped at this locus in families A and B, respectively. DNA sequence analysis of six candidate genes (PLEKHG7, SLC6A15, VEZT, DUSP6, KERA and KITLG), located in the linkage interval on chromosome 12q21.2-q22, failed to detect potential sequence variants in the affected individuals of the two families. However, DNA sequence analysis of CDH3 gene, located on chromosome 16q21-q23.1, detected a single base pair homozygous insertion (c.1024_1025insG and p.342insGfsX345) in exon 9 in family A and deletion of four base pair (c.1859_1862delCTCT and p.620delSfsX629) in exon 13 in family B. We described for the first time digenic inheritance of an autosomal recessive hypotrichosis phenotype in two unlinked loci on chromosomes 12q21.2-q22 and 16q21-q23.1 in two unrelated consanguineous Pakistani families.
毛发稀少症是一种人类遗传性脱发疾病，受影响的个体表现为头皮和/或身体其他部位毛发稀疏甚至完全缺失。迄今为止，至少有八个孤立的常染色体隐性和显性毛发稀少症基因座已被定位在不同的人类染色体上，并且相应的基因也已被确定。本文对两个近亲家族（A 和 B）中观察到的遗传性毛发稀少症进行了详细的临床和分子研究。使用 >500 个高度多态性微卫星标记进行人类基因组扫描，在两个家族中均发现染色体 12q21.2-q22 和 16q21-q23.1 上的毛发稀少表型存在相同的连锁证据。12q21.2-q22 上的新毛发稀少基因座跨越 16.3cM（17.62Mb），由标记 D12S326 和 D12S101 侧翼。在该基因座上，家族 A 和 B 分别获得了最大多点对数优势比（LOD）评分 3.68 和 3.31。在两个家族中鉴定出的 16q21-q23.1 上的第二个毛发稀少基因座跨越 5.58cM（8.28Mb），由标记 D16S3031 和 D16S512 侧翼。在家族 A 和 B 中，标记映射在该基因座上获得了最大多点 LOD 评分 3.17 和 3.31。位于染色体 12q21.2-q22 连锁区间内的六个候选基因（PLEKHG7、SLC6A15、VEZT、DUSP6、KERA 和 KITLG）的 DNA 序列分析未能在两个家族的受影响个体中检测到潜在的序列变异。然而，位于染色体 16q21-q23.1 上的 CDH3 基因的 DNA 序列分析在家族 A 中检测到外显子 9 中单个碱基对纯合插入（c.1024_1025insG 和 p.342insGfsX345），在家族 B 中外显子 13 中检测到四个碱基对缺失（c.1859_1862delCTCT 和 p.620delSfsX629）。我们首次描述了两个不相关的近亲巴基斯坦家族中，位于染色体 12q21.2-q22 和 16q21-q23.1 上的两个独立隐性毛发稀少表型的双基因遗传。
