Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS. Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected. The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed. Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years. The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively. The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(r=0.234,P=0.023),palmoplantar keratoderma(r=0.325,P=0.001),webbing/pseudoainhum(r=0.247,P=0.016),dysphagia(r=0.333,P=0.001),urethral stricture(r=0.280,P=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(χ²=11.292,P=0.001)and anal stenosis(χ²=4.014,P=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%. The gene mutation site had no significant correlation with squamous cell carcinoma or patient country. Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).
Adolescent ; Adult ; Ainhum ; Blister ; Carcinoma, Squamous Cell ; Child ; Constriction, Pathologic ; Deglutition Disorders/complications* ; Epidermolysis Bullosa ; Female ; Humans ; Inflammation ; Keratoderma, Palmoplantar/complications* ; Male ; Membrane Proteins ; Mutation ; Neoplasm Proteins/genetics* ; Periodontal Diseases ; Photosensitivity Disorders ; Urethral Stricture/complications* ; Young Adult

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient featuring autosomal dominant Olmsted syndrome. METHODS: Clinical features of the patient was reviewed. High-throughput sequencing was carried out to detect potential genetic variants. RESULTS: The proband, a 12-year-old girl, featured excessive keratinization on hands and feet, contracture of finger joints, and abnormal position and residual contraction of the fifth toes. Skin biopsy showed significant hyperkeratosis, epidermal hyperplasia, and mild interepidermal cell edema. A de novo heterozygous missense variant c.2016G>T(p.Met672Ile) was identified in the TRPV3 gene by high-throughout sequencing. The result was verified by Sanger sequencing. CONCLUSION The destructive palmoplantar keratosis in the child may be attributed to the c.2016G>T(p.Met672Ile) variant of the TRPV3 gene. Aboving finding has provided new evidence for the correlation of genetic variants with clinical phenotypes of Olmsted syndrome.
Child ; Female ; Heterozygote ; Humans ; Keratoderma, Palmoplantar/genetics* ; Skin ; Syndrome ; TRPV Cation Channels/genetics*

Desmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels. DSP is essential for normal myocardial development and the maintenance of its structural functions. Studies have suggested that DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM), left ventricular noncompaction, and is also closely associated with the Carvajal syndrome, Naxos disease, and erythro-keratodermia-cardiomyopathy syndrome with skin and heart damage. The structure and function of DSP, as well as the clinical manifestations of DSP-related cardiomyopathy were reviewed in this article.
Arrhythmogenic Right Ventricular Dysplasia ; Cardiomyopathies/genetics* ; Desmoplakins/genetics* ; Hair Diseases ; Humans ; Keratoderma, Palmoplantar

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