A study of phenotypic correlation with the genotypic status of HTM regions of KRTHB6 and KRTHB1 genes in monilethrix families of Indian origin

Sujay Khandpur , N.K. Bairwa , B.S.N. Reddy , R. Bamezai
{"title":"A study of phenotypic correlation with the genotypic status of HTM regions of KRTHB6 and KRTHB1 genes in monilethrix families of Indian origin","authors":"Sujay Khandpur ,&nbsp;N.K. Bairwa ,&nbsp;B.S.N. Reddy ,&nbsp;R. Bamezai","doi":"10.1016/j.anngen.2003.07.003","DOIUrl":null,"url":null,"abstract":"<div><p>We investigated 21 affected individuals in two unrelated monilethrix families of Indian origin and identified point mutation (g.4624G&gt;A) in the HTM motif (exon-7) of the KRTHB6 gene in all the affected members leading to E413K change in this basic keratin. The HTM motif of KRTHB1, however, showed previously unreported two allelic variants, one with three novel variations (SNPs) in <em>cis</em>: g.4421insT (intronic); g.4461T&gt;C (exonic); g.4485A&gt;G (exonic) and second with only intronic variation (SNP) (g.4421insT). Interestingly, the two distinct phenotypes of: localized severe hair defect with beaded appearance confined to the scalp of all the affected members of Family 1 and of generalized unbeaded hair defect of moderate severity in Family 2, segregated in the two families, respectively, correlating with the two separate genotypes for the functionally critical HTM region of KRTHB1 gene in the background of E413K mutation in the KRTHB6 gene. Presence of E413K mutation in the HTM of KRTHB6 gene was not observed in the background of the allelic variant with three SNPs in KRTHB1 gene in homozygous condition in all the affected members of Family 1, affected with a localized but severe form of the disease. However, the same (E413K) mutation existed in the KRTHB6 gene in the background of the allelic variant with three SNPs in the KRTHB1 gene in homozygous condition, consistently in all the affected members of Family 2, where all its affected members showed the segregation of a milder form of the disease. Presence of both E413K mutation in the KRTHB6 and the variations in the KRTHB1 genes were not observed together in randomly selected 150 unaffected controls outside the two affected families. This is also the first report of HTM mutation of KRTHB6 gene in monilethrix cases of Indian origin and the first report of SNPs in the KRTHB1 gene in literature to our knowledge.</p></div>","PeriodicalId":100089,"journal":{"name":"Annales de Génétique","volume":"47 1","pages":"Pages 77-84"},"PeriodicalIF":0.0000,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.anngen.2003.07.003","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annales de Génétique","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0003399503000704","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 4

Abstract

We investigated 21 affected individuals in two unrelated monilethrix families of Indian origin and identified point mutation (g.4624G>A) in the HTM motif (exon-7) of the KRTHB6 gene in all the affected members leading to E413K change in this basic keratin. The HTM motif of KRTHB1, however, showed previously unreported two allelic variants, one with three novel variations (SNPs) in cis: g.4421insT (intronic); g.4461T>C (exonic); g.4485A>G (exonic) and second with only intronic variation (SNP) (g.4421insT). Interestingly, the two distinct phenotypes of: localized severe hair defect with beaded appearance confined to the scalp of all the affected members of Family 1 and of generalized unbeaded hair defect of moderate severity in Family 2, segregated in the two families, respectively, correlating with the two separate genotypes for the functionally critical HTM region of KRTHB1 gene in the background of E413K mutation in the KRTHB6 gene. Presence of E413K mutation in the HTM of KRTHB6 gene was not observed in the background of the allelic variant with three SNPs in KRTHB1 gene in homozygous condition in all the affected members of Family 1, affected with a localized but severe form of the disease. However, the same (E413K) mutation existed in the KRTHB6 gene in the background of the allelic variant with three SNPs in the KRTHB1 gene in homozygous condition, consistently in all the affected members of Family 2, where all its affected members showed the segregation of a milder form of the disease. Presence of both E413K mutation in the KRTHB6 and the variations in the KRTHB1 genes were not observed together in randomly selected 150 unaffected controls outside the two affected families. This is also the first report of HTM mutation of KRTHB6 gene in monilethrix cases of Indian origin and the first report of SNPs in the KRTHB1 gene in literature to our knowledge.

印度单孢菌科KRTHB6和KRTHB1基因HTM区表型与基因型状态的相关性研究
我们调查了21个来自两个不相关的印度裔单胞菌家族的受影响个体,并在所有受影响成员中发现了KRTHB6基因HTM基元(外显子7)的点突变(g.4624G>A),导致该基本角蛋白E413K发生变化。然而,KRTHB1的HTM基序显示出先前未报道的两个等位基因变异,其中一个具有三个顺式的新变异(SNPs): g.4421insT(内含子);g.4461T> C(其实);G . 4485a>G(外显子),第二种只有内含子变异(SNP) (G . 4421inst)。有趣的是,在KRTHB6基因E413K突变的背景下,KRTHB1基因功能关键HTM区域的两种不同的基因型分别在两个家族中分离出来,这两种不同的表型分别是:家族1中所有受影响成员局限于头皮的局限性严重头发缺陷,以及家族2中中度严重的全身性无头发缺陷。在KRTHB6基因HTM存在E413K突变的背景下,在KRTHB1基因的三个snp等位变异纯合的情况下,所有家族1的患病成员都患有局限性但严重的疾病。然而,KRTHB6基因中存在相同的(E413K)突变,在KRTHB1基因纯合状态下具有三个snp的等位基因变异的背景下,在Family 2的所有受影响成员中一致存在,其中所有受影响成员都表现出较轻形式的疾病分离。在两个受影响家庭之外的随机选择的150名未受影响的对照中,没有观察到KRTHB6中E413K突变和KRTHB1基因突变的同时存在。这也是据我们所知文献中首次报道的印度源单胞菌病例中KRTHB6基因的HTM突变,以及KRTHB1基因snp的报道。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信