title: KRT9 gene mutation as a reliable indicator in the prenatal molecular diagnosis of epidermolytic palmoplantar keratoderma.
abstract: Epidermolytic palmoplantar keratoderma (EPPK) is the most frequent form of such keratodermas. It is inherited in an autosomal dominant pattern and is clinically characterized by diffuse yellowish thickening of the skin on the palms and soles with erythematous borders during the first weeks or months after birth. EPPK is generally caused by mutations of the KRT9 gene. More than 26 KRT9 gene mutations responsible for EPPK have been described (Human Intermediate Filament Database, www.interfil.org), and many of these variants are located within the highly-conserved coil 1A region of the α-helical rod domain of keratin 9. Unfortunately, there is no satisfactory treatment for EPPK. Thus, prenatal molecular diagnosis or pre-pregnancy diagnosis is crucial and benefits those affected who seek healthy descendants. In the present study, we performed amniotic fluid-DNA-based prenatal testing for three at-risk pregnant EPPK women from three unrelated southern Chinese families who carried the KRT9 missense mutations p.Arg163Trp and p.Arg163Gln, and successfully helped two families to bear normal daughters. We suggest that before the successful application of preimplantation genetic diagnosis (PGD), and noninvasive prenatal diagnosis of EPPK that analyzes fetal cells or cell-free DNA in maternal blood, prenatal genetic diagnosis by amniocentesis or chorionic villus sampling (CVS) offers a quite acceptable option for EPPK couples-at-risk to avoid the birth of affected offspring, especially in low- and middle-income countries.
authors.affiliation: Department of Biology, Ningbo College of Health Sciences, Ningbo, Zhejiang Province 315100, China; Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
authors.forename: Hai-Ping
authors.initials: HP
authors.lastname: Ke
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
authors.forename: Hu-Ling
authors.initials: HL
authors.lastname: Jiang
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
authors.forename: Ya-Su
authors.initials: YS
authors.lastname: Lv
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Huang
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
authors.forename: Zhen-Fang
authors.initials: ZF
authors.lastname: Du
authors.affiliation: Key Laboratory of Reproductive Genetics (Zhejiang), Ministry of Education, and Centre of Reproductive Medicine, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310006, China.
authors.forename: Yu-Qin
authors.initials: YQ
authors.lastname: Luo
authors.affiliation: Key Laboratory of Reproductive Genetics (Zhejiang), Ministry of Education, and Centre of Reproductive Medicine, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310006, China.
authors.forename: Chen-Ming
authors.initials: CM
authors.lastname: Xu
authors.affiliation: Department of Gynaecology and Obstetrics, Ningbo Women and Children's Hospital, Ningbo, Zhejiang Province 315012, China.
authors.forename: Qi-Hui
authors.initials: QH
authors.lastname: Fan
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center of Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China. Electronic address: zhangxianning@zju.edu.cn.
authors.forename: Xian-Ning
authors.initials: XN
authors.lastname: Zhang
mesh_terms: D000328:Adult; D015193:Chorionic Villi Sampling; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D053534:Keratin-9 / Q000235:genetics*; D053546:Keratoderma, Palmoplantar, Epidermolytic / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: C507440:KRT9 protein, human; D053534:Keratin-9
keywords: Amniocentesis; Epidermolytic palmoplantar keratoderma; KRT9 gene; Mutation; Prenatal genetic diagnosis