Adult ; Child ; Female ; Humans ; Keratoderma, Palmoplantar ; genetics ; pathology ; Male ; Pedigree

Olmsted syndrome (OS) is a rare congenital skin disorder characterized by severe palmoplantar and periorificial keratoderma, alopecia, onychodystrophy, and severe pruritus. Recently, pathogenic ‘gain-of-function‘ mutations of the transient receptor potential vanilloid 3 gene (TRPV3), which encodes a cation channel involved in keratinocyte differentiation and proliferation, hair growth, inflammation, pain and pruritus, have been identified to cause OS. Due to the rarity, the pattern of inheritance of OS is still unclear. We report a case of OS in a 3-year-old Korean girl and its underlying gene mutation. The patient presented with a disabling, bilateral palmoplantar keratoderma with onychodystrophy. She also exhibited pruritic eczematous skin lesions around her eyes, ears and gluteal fold. Genetic analysis identified a heterozygous p.Gly568Val missense mutation in the exon 13 of TRPV3. To our knowledge, this is the first case of OS in the Korean population showing a missense mutation p.Gly573Ser.
Abnormalities, Multiple/*genetics ; Base Sequence ; Child, Preschool ; Female ; Heterozygote ; Humans ; Keratoderma, Palmoplantar/genetics ; Lipid Droplets/ultrastructure ; Mutation, Missense/*genetics ; Skin/pathology/ultrastructure ; Syndrome ; TRPV Cation Channels/*genetics

OBJECTIVETo analyze the clinical characteristics and causative mutation in an ethnic Han Chinese family affected with punctate palmoplantar keratoderma (PPPK).

METHODSClinical characteristics and inheritance pattern of the family were analyzed. Two seriously affected individuals from the family were investigated by whole exome sequencing. Three healthy individuals from the family and 120 non-PPPK individuals were evaluated to validate the result.

RESULTSThe family was characterized by keratotic papules on the palms and soles, which gradually increased in size and number with age and coalesced with each other, particularly over the pressure part of the palms and soles. The family has featured autosomal dominant inheritance. A heterozygous frameshift variant c.419delC in exons of the CELA1 gene was identified in all affected individuals but not among non-affected members.

CONCLUSIONA heterozygous frameshift variant c.419delC in CELA1 gene probably underlies the disease in the family affected with PPPK.

Adult ; Base Sequence ; Female ; Frameshift Mutation ; Heterozygote ; Humans ; Keratoderma, Palmoplantar ; genetics ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation ; Pancreatic Elastase ; genetics ; Pedigree ; Young Adult

Adult ; Female ; Humans ; Keratin-1 ; genetics ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar ; genetics ; Male ; Middle Aged ; Pedigree

OBJECTIVETo analyze potential mutation in keration 9 (KRT9) gene in a large Chinese family with epidermolytic palmoplantar keratoderma (EPPK) and to perform prenatal diagnosis on the fetus at 10th gestational week.

METHODSPeripheral venous blood samples were obtained from 5 affected and 8 unaffected individuals of the family. Fifty unrelated healthy individuals were also recruited as controls. PCR was used to amplify exons 1 and 6 of KRT9 gene, and the products were sequenced directly. After the mutation was confirmed, prenatal diagnosis was performed on the fetus during the first trimester of pregnancy.

RESULTSA heterozygous missense mutation c.482A to G in the KRT9 gene, which has led to substitution of Asparaginate by Serine at codon 161 (p.N161S), was detected in all patients but not in other individuals of the family and the 50 healthy controls. The fetus was found to have carried the p.N161S mutation too. Following selected abortion, analysis of fetal tissue was consistent with prenatal diagnosis.

CONCLUSIONThe missense mutation c.482A to G (p.N161S), which has been shown previously to cause EPPK, is found in the KRT9 gene of patients in this family. Gene mutation analysis for prenatal diagnosis is efficient to facilitate detection of affected fetus in time.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA Mutational Analysis ; methods ; Humans ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar, Epidermolytic ; diagnosis ; genetics ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Prenatal Diagnosis ; methods

OBJECTIVE: Mutations in the GJB2 are the most common cause of nonsyndromic autosomal recessive sensorineural hearing loss. A few mutations in GJB2 have also been reported to cause dominant nonsyndromic or syndromic hearing loss. This study analysised the GJB2 dominant mutation in Chinese deafness. METHOD: 1641 patients as GJB2-related hearing loss were enrolled, summarized the type of dominant mutaion, analyzed the hearing level and other systerm lesion. RESULT: Nine probands with severe-profound hearing loss were diagnosed as GJB2 domiant mutation (R75W,G130V, R143Q,p. R184Q). And one patient with R75W mutation was diagosed as hearing loss and palmoplantar keratoderma. CONCLUSION GJB2 dominant mutation can cause severe-to-profound bilateral sensorineural hearing impairment and not common with syndromic hearing loss in Chinese deafness.
Asian Continental Ancestry Group ; Connexin 26 ; Connexins ; genetics ; Deafness ; genetics ; Hearing Loss ; Hearing Loss, Sensorineural ; Humans ; Keratoderma, Palmoplantar ; Mutation ; Phenotype

OBJECTIVETo detect potential mutations of gap junction protein beta 2 (GJB2) and loricrin (LOR) genes in two patients with Vohwinkel syndrome.

METHODSPolymerase chain reaction and DNA sequencing were used for detecting potential mutations in the GJB2 and LOR genes. Parents of one patient and 50 healthy individuals were used as controls.

RESULTSA novel homozygous missense mutation (c.A796G) of LOR gene was detected in one patient. The same mutation was not found in the other patient, their relatives and the 50 healthy controls.

CONCLUSIONA missence mutation of LOR gene was detected in a patient with Vohwinkel syndrome.

Abnormalities, Multiple ; genetics ; pathology ; Adult ; Child, Preschool ; Connexin 26 ; Connexins ; genetics ; Female ; Hand Deformities, Congenital ; genetics ; pathology ; Hearing Loss, Sensorineural ; genetics ; pathology ; Humans ; Keratoderma, Palmoplantar ; genetics ; pathology ; Male ; Membrane Proteins ; genetics ; Mutation, Missense ; Sequence Analysis, DNA

OBJECTIVETo analyze potential mutation of keration 9 gene (KRT9) in a Chinese family affected with epidermolytic palmoplantar keratoderma (EPPK) and to correlate genotype with the phenotype.

METHODSGenomic DNA was extracted from peripheral blood samples of 12 patients and 13 healthy individuals from the family and 100 unrelated individuals. Polymerase chain reaction (PCR) was used to amplify exons 1 and 6 of KRT9 gene. PCR products were sequenced bidirectionally in order to identify potential mutations.

RESULTSA heterozygous transversional mutation, 488G→A, was identified in exon 1 of KRT9 gene in all patients, which has resulted in substitution of a glutamine residue for arginine acid at position 163 (R163Q) of the KRT9 protein. The same mutation was not found in the 13 healthy members from the family and 100 unrelated individuals.

CONCLUSIONThe 488G→A mutation of KRT9 gene is probably the cause of EPPK in this Chinese family.

Adult ; Base Sequence ; DNA Mutational Analysis ; methods ; Female ; Humans ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar, Epidermolytic ; genetics ; Male ; Molecular Sequence Data ; Mutation

Gap junctions, which mediate rapid intercellular communication, consist of connexins, small transmembrane proteins that belong to a large family of proteins found throughout the species. Mutations in the GJB2 gene, encoding Connexin 26, can cause nonsyndromic autosomal recessive or dominant hearing loss with or without skin manifestations. A 3-yr-old Korean female and her mother presented to our clinic with diffuse hyperkeratosis of the palms and soles (May 3, 2007). Skin biopsies from the soles of both patients demonstrated histopathological evidence of palmoplantar keratoderma. The patient and a number of her maternal family members also had congenital hearing loss. The combination of congenital hearing loss and palmoplantar keratoderma, inherited as an autosomal dominant trait, led us to test for a mutation in the GJB2 gene in both patients. The results showed the R75W mutation of the GJB2 gene in both. In conclusion, the simultaneous occurrence of a GJB2 mutation in a mother and daughter suggests that R75W mutation cause autosomal dominant hearing loss presenting with palmoplantar keratoderma. To the best of our knowledge, this is the first report of a GJB2 mutation associated with syndromic autosomal dominant hearing loss and palmoplantar keratoderma in a Korean family.
Adult ; Alleles ; Amino Acid Substitution ; Child, Preschool ; Connexins/*genetics ; DNA Mutational Analysis ; Deafness/complications/*genetics ; Female ; Humans ; Keratoderma, Palmoplantar/complications/*genetics/pathology ; *Mutation ; Pedigree ; Skin/pathology

OBJECTIVETo map and identify the disease gene for the epidermolytic palmoplantar keratoderma (EPPK) in a Uighur family of China.

METHODSBlood samples were collected and genomic DNA was extracted from 48 members of the Xinjiang Uighur family. Six microsatellite repeat sequences on chromosome region 17q12-q21 and 12q13 were selected based on the two known candidate genes KRT9 and KRT1. Two-point linkage analysis and haplotype analysis were performed. Exons and their flanking intronic sequence of the KRT9 gene were amplified by polymerase chain reaction (PCR) and sequenced.

RESULTSData from the marker D17S1787 suggested linkage and yielded a Lod score of 8.65 at theta=0 by using MLINK software. Genotypes and haplotypes were acquired. The disease gene of the EPPK family is located between markers 17/TG/36620115 and D17S846. Chromosome 12q13 region was excluded with the negative Lod score obtained in marker D12S96 (Lod=-infinity at theta=0). No pathogenic mutation was detected in the KRT9 gene.

CONCLUSIONThe disease gene of the EPPK family is located on chromosome region 17q21.2. The keratin 9 gene might not be the disease gene.

China ; Chromosomes, Human, Pair 17 ; genetics ; Female ; Humans ; Keratin-1 ; genetics ; Keratin-9 ; genetics ; Keratoderma, Palmoplantar, Epidermolytic ; ethnology ; genetics ; Male ; Microsatellite Repeats ; Mutation ; Pedigree