Highly prevalent LIPH founder mutations causing autosomal recessive woolly hair/hypotrichosis in Japan and the genotype/phenotype correlations.
Highly prevalent LIPH founder mutations causing autosomal recessive woolly hair/hypotrichosis in Japan and the genotype/phenotype correlations.
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DOI：
10.1371/journal.pone.0089261
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Akiyama M
中科院分区：
文献类型：
--
作者：
Tanahashi K;Sugiura K;Kono M;Takama H;Hamajima N;Akiyama M
LIPH突变导致常染色体隐性羊毛/毛少症（ARWH）， 2个错义突变c.736T>A （p.Cys246Ser）和c.742C>A （p.His248Asn）被认为是日本人群中ARWH的普遍创始突变。目的揭示日本ARWH病例的基因型/表型相关性以及来自14个无亲缘关系日本家庭的14例日本患者的单倍型。13例患者有羊毛状毛发，1例患者出生后完全秃顶。LIPH突变搜索在10例患者中发现纯合子c.736T>A突变。c.736T>A和c.742C>A复合杂合突变3例，c.742C>A纯合突变1例。轻度毛少症的表型仅限于纯合子c.736T . >A突变患者。只有1例纯合子c.742C>A患者出现严重的完全性秃顶表型。单倍型分析显示，含有LIPH c.736T>A突变的等位基因具有与先前报道的单倍型相同的单倍型，尽管含有LIPH c.742C>A突变的5条染色体中有4条等位基因具有与先前报道的创始等位基因不同的单倍型。这些带有c.742C>A的等位基因被认为是导致ARWH的第三个创始LIPH突变。为了准确确定创始突变的患病率，我们调查了819名日本对照中这些突变的等位基因频率。c.736T>A杂合突变13例（等位基因频率为0.0079，载体率为0.016），c.742C>A杂合突变2例（等位基因频率为0.0012，载体率为0.0024）。总之，本研究证实了LIPH致病性始创突变的更准确的等位基因频率，并表明日本存在第三个始创突变。此外，目前的研究结果表明，LIPH的突变模式可能与ARWH中毛少的严重程度有关。
Mutations in LIPH cause of autosomal recessive woolly hair/hypotrichosis (ARWH), and the 2 missense mutations c.736T>A (p.Cys246Ser) and c.742C>A (p.His248Asn) are considered prevalent founder mutations for ARWH in the Japanese population. To reveal genotype/phenotype correlations in ARWH cases in Japan and the haplotypes in 14 Japanese patients from 14 unrelated Japanese families. 13 patients had woolly hair, and 1 patient had complete baldness since birth. An LIPH mutation search revealed homozygous c.736T>A mutations in 10 of the patients. Compound heterozygous c.736T>A and c.742C>A mutations were found in 3 of the patients, and homozygous c.742C>A mutation in 1 patient. The phenotype of mild hypotrichosis with woolly hair was restricted to the patients with the homozygous c.736T>A mutation. The severe phenotype of complete baldness was seen in only 1 patient with homozygous c.742C>A. Haplotype analysis revealed that the alleles containing the LIPH c.736T>A mutation had a haplotype identical to that reported previously, although 4 alleles out of 5 chromosomes containing the LIPH c.742C>A mutation had a different haplotype from the previously reported founder allele. These alleles with c.742C>A are thought to be the third founder LIPH mutation causing ARWH. To accurately determine the prevalence of the founder mutations, we investigated allele frequencies of those mutations in 819 Japanese controls. Heterozygous c.736T>A mutations were found in 13 controls (allele frequency: 0.0079; carrier rate: 0.016), and heterozygous c.742C>A mutations were found in 2 controls (allele frequency: 0.0012; carrier rate: 0.0024). In conclusion, this study confirms the more accurate allele frequencies of the pathogenic founder mutations of LIPH and shows that there is a third founder mutation in Japan. In addition, the present findings suggest that the mutation patterns of LIPH might be associated with hypotrichosis severity in ARWH.
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