A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1

Abstract Background Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. Objective The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. Methods In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. Results The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. Study limitation Gene expression studies are absent that would have strengthened the findings of computational analysis. Conclusion The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.

Familial Pityriasis Rubra Pilaris in Siblings / 대한피부과학회지

No abstract available.

A Case of Costello Syndrome with Severe Palmoplantar Keratoderma / 대한피부과학회지

No abstract available.

Analysis of KRT9 gene mutation in Chinese Han population / 上海交通大学学报（医学版）

Objective • To explore the main mutation types and pathogenicity of the coding region of keratin 9 gene (KRT9) in Chinese Han population, and to provide reference information for the classification and prediction of clinical diagnosis of the disease with epidermolytic palmoplantar keratoderma (EPPK). Methods • 834 subjects were recruited from 278 families that were not affected by EPPK in the Chinese Han population. The mutations in the coding region of KRT9 gene were detected by using the next-generation sequencing (NGS)-based gene panel combined with Sanger sequencing. The pathogenicity analysis of variants was performed by using SIFT and Polyphen-2 prediction software. Results • A total of twelve KRT9 gene mutations were detected in the Chinese Han population based on 834 individuals from 278 families. Among the twelve different mutations, six synonymous mutations and six missense mutations were identified, respectively. The assessment of pathogenicity of KRT9 gene variants was analyzed by bioinformatics tools, such as SIFT and Polyphen-2 prediction, conservative analysis, and database query. Furthermore, these missense mutations were classified as benign or possibly benign variants. Conclusion • In this study, six missense mutations in the coding region of KRT9 gene exon were detected in the Chinese Han population. According to the American Society of Medical Genetics and Genomics (ACMG) variant classification guide, all the six variants were benign or possibly benign. However, previous reports have found that a KRT9 c.1216T>C (p.C406R) mutation was pathogenic in a pedigree with EPPK, which were inconsistent with our findings, and the pathogenicity of this mutation still has to be verified by further functional experiments.

A Case of Palmoplantar Keratoderma Presenting as Multiple Cutaneous Horns / 대한피부과학회지

No abstract available.

Do you know this syndrome? Clouston syndrome

Abstract Ectodermal dysplasias are conditions that present primary defects in two or more tissues of ectodermal origin and can be classified as hypohidrotic and hidrotic. Hidrotic ectodermal dysplasia or Clouston syndrome is an autosomal dominant genodermatosis and appears as a triad of clinical findings: palmoplantar keratoderma, nail dystrophy, and hypotrichosis. The hair is sparse and brittle. The nails become thickened and dystrophic, which is an essential characteristic of the syndrome. The diagnosis is made based on clinical findings. This study reports a case of a patient who began with changes in hair, nails and palmoplantar keratoderma in early childhood.

Malnutrition-induced Acquired Palmoplantar Keratoderma: A Case Report / 대한피부과학회지

Palmoplantar keratoderma is characterized clinically by excessive thickening of the skin and histologically by hyperkeratosis on the palms and soles. It can be classified based on inheritance patterns, causes, clinical presentation, and extent of involvement. Acquired palmoplantar keratoderma shows multifactorial etiology including exposure to certain chemicals or drugs, metabolic disorders, malnutrition, systemic disease, malignancy, dermatosis, and/or infection. We report a rare case of acquired palmoplantar keratoderma induced by malnutrition.

Osteoartropatía hipertrófica primaria y queratodermia palmoplantar: a propósito de un caso / Primary hypertrophic osteoarthropathy and palmoplantar keratoderma: a case report

La acropaquia es un trastorno que puede presentarse en forma aislada o formar parte del síndrome de osteoartropatía hipertrófica, entidad caracterizada por periostosis, dolor articular y acropaquia. Cuando este síndrome es causado por una mutación genética específica, se denomina osteoartropatía hipertrófica primaria. Este raro desorden hereditario se asocia, además, a alteraciones dermatológicas típicas, como hiperseborrea, acné, engrosamiento de pliegues faciales, entre otras. Una asociación rara vez descrita es la queratodermia palmoplantar. Se presenta el caso de una mujer de 46 años con osteoartropatía hipertrófica primaria asociada a queratodermia palmoplantar que asistió a la unidad de dermatología del Hospital Gustavo Fricke, Viña del Mar, Chile.

Clubbing is a disorder that can be an isolated finding or be part of the hypertrophic osteoarthropathy syndrome, an entity characterized by periostosis, joint pain and clubbing. When this syndrome is caused by a specific genetic mutation, it is called primary hypertrophic osteoarthropathy. This rare hereditary disorder is also associated with typical dermatological findings, such as hyperseborrhea, acne and facial feature coarsening. An association rarely described is palmoplantar keratoderma. We present the case of a 46-year-old woman with primary hypertrophic osteoarthropathy and palmoplantar keratoderma who came to the dermatology unit of Gustavo Fricke Hospital, Viña del Mar, Chile.

Pachyonychia Congenita Type II: A Case Report

Pachyonychia congenita type II is an autosomal dominant inherited rare genodermatosis characterized by dystrophic wedge shaped thickened nails with subungual hyperkeratosis, symmetric palmoplantar keratoderma, steatocystoma multiplex. Here we report a 23-year-old male with characteristic features of dystrophic nails, palmoplantar keratoderma, steatocystoma multiplex, follicular hyperkeratotic papules and history of natal teeth at birth.

Clouston's Syndrome—A Case Report

Clouston's syndrome or Hidrotic ectodermal dysplasia is an autosomal-dominant inherited rare ectodermal dysplastic disorder characterized by triad of nail dystrophy, palmoplantar keratoderma, and alopecia. Here we present a case report of clouston syndrome with classical triad along with hypodontia, microdontia and severe mental retardation. This is being reported because of it is rarity.

Unilateral linear punctate palmoplantar keratoderma.

Punctate palmoplantar keratoderma (Brauer-Buschke-Fischer syndrome) is a rare entity. Among punctate keratoderma, the linear presentation is much rarer, and exact incidence is not known. Unilateral linear punctate palmoplantar keratoderma is not yet reported in the literature. Here we report a case 12-year-old child presented with asymptomatic linear punctate plaque on the left sole and hand; histology revealed hyperkeratotic epidermis without columns of parakeratosis or cornoid lamella.

Ectodermal dysplasia-skin fragility syndrome.

Ectodermal dysplasia-skin fragility (EDSF) syndrome is a rare and first described inherited disorder of desmosomes. It occurs due to loss-of-function mutations in PKP1 gene resulting in poorly formed desmosomes and loss of desmosomal and epidermal integrity. We report a case of a 2-year-old Indian male child who presented with palmoplantar hyperkeratosis with fissuring, short, sparse, and easily pluckable scalp hair, nail dystrophy, and multiple erosions over the skin. Skin biopsy showed epidermal hyperplasia with widening of intercellular spaces. His developmental milestones were delayed but intelligence was normal. Echocardiography, X-ray chest, and electrocardiogram were normal. Very few cases of this syndrome have been reported in the literature. We consider this as the first case report from India.

A Sporadic Case of Mal de Meleda Caused by Gene Mutation in SLURP-1 in Korea

Mal de Meleda (MDM), also known as keratoderma palmoplantaris transgrediens, is a rare inherited form of palmoplantar keratoderma. It is characterized by erythema and hyperkeratosis of the palms and soles, extending to the dorsal aspects of the hands and feet. A 15-year-old Korean female presented with sharply demarcated hyperkeratotic plaques on the palms and soles, which extended to the dorsal surfaces of the hands and feet, in a "glove-and-socks" distribution. The histopathologic study showed marked hyperkeratosis, acanthosis, and normogranulosis, without epidermolysis. Her genetic study detected compound heterozygous mutation in exon 3 of the ARS gene encoding SLURP-1. Family history did not reveal any other affected members and no consanguineous relationship was found. In view of these findings, we diagnosed this case as the first reported sporadic case of MDM in Korea, the farthest location from the endemic island of Meleda.

Woolly hair generalizado: caso clínico e revisão da literatura / Generalized woolly hair: case report and literature review

O termo woolly hair, ou cabelo lanoso, refere-se a uma variante anormal de cabelo, que pode ser parcial ou generalizado. As variantes de woolly hair generalizado são raras e podem ocorrer isoladamente ou associadas a outras alterações cutâneas e extracutâneas. Desta forma, nestes doentes, é necessário a exclusão de certos síndromes, como o de Noonan e cardiofaciocutâneo (CFC), que cursam com importante morbilidade e mortalidade. É descrito o caso clínico de uma criança com woolly hair generalizado e queratose pilar, mas que, após avaliação dos vários órgãos e sistemas, não foi encontrada qualquer alteração ou característica associada a esses síndromes.

The term woolly hair, or tightly curled hair, refers to a structural anomaly of scalp hair, which can be partial or generalized. Generalized woolly hair variants are rare and can occur in isolation or in association with other cutaneous and extra-cutaneous abnormalities. Thus, it is important to dismiss in these patients the diagnosis of syndromes such as the Noonan syndrome and Cardiofaciocutaneous syndrome, which have high morbidity and mortality rates. We report the clinical case of a 7 year-old boy with generalized woolly hair and keratosis pilaris. After an evaluation of organs and systems, no alteration or characteristics associated with these syndromes were found.

Localization of the disease-causing gene coding for hereditary palmoplantar keratoderma / 基础医学与临床

Objective To identify a locus at chromosome coding for hereditary palmoplantar keratoderma of three Chinese pedigrees.Methods The genome scan was conducted with microsatellite markers on chromosome 12(D12S85、D12S368、D12S83、D12S345)and 17(D17S1868、D17S787、D17S1857、D17S798、D17S944、D17S949)respectively on the ABI 3100 Genetic Analyzer(Applied Biosystems).Two-point LOD score was calculated.Results The maximum two-point LOD score 6.59 and 5.96 at ?=0.1 were obtained at D17S1868 and D17S787 on chromosome 17q12～q21.It is an evidence of linkage between this disease and KRT9 which has been mapped within the region.Conclusion There is a locus responsible for this disease on chromosome 17q12～q21.

A Sporadic Case of Punctate Palmoplantar Keratoderma / 대한피부과학회지

Punctate palmoplantar keratoderma(PPK) is a rare disease, characterized by small, hard hyperkeratotic papules which are irregularly distributed on the palms and soles. PPK is an autosomal dominant disease with variable penetrance. We report a case of sporadic case of punctate palmoplantar keratoderma in a 26-year-old female patient.

A Case of Epidermolytic Palmoplantar Keratoderma / 대한피부과학회지

Palmoplantar keratodermas are divided into autosomal dominant and autosomal recessive groups by the mode of transmission. The autosomal dominantly transmitted group is further divided into epidermolytic and nonepidermolytic types according to the histological findings. Hereditary epidermolytic palmoplantar keratoderma manifests clinically as a localized thickening of the palms and soles. Herein we report a 29-year-old woman showing the typical clinical and histologic features of epidermolytic palmoplantar keratoderma without family history. This case could be spontaneous mutations that will later breed a true autosomal dominant trait.

A Case of Punctate Palmoplantar Keratoderma / 대한피부과학회지

Punctate palmoplantar keratoderma(PPK) is an autosomal dominantly transmitted disease with variable penetrance. Clinically there are multiple tiny punctate keratoses over the entire palmoplantar surfaces. Lesions are discrete and diffuse, and may be symmetrical. There have been occasional reports of families with autosomal dominant transmission of punctate PPK and internal malignancies or spastic paralysis. We report a case of punctate palmoplantar keratoderma with severe periodontitis in 60-year-old male patient.

A case of Hereditary Epidermolytic Palmoplantar Keratoderma / 대한피부과학회지

The hereditary epidermolytic palmoplantar keratoderma (Vorner"s kerato derma) is characterized by autosomal dominantly inherited, marked, symmetrical thickening of the palms and soles. The presence of epidermolytic hyperkeratosis in skin biopsy differentiates hereditary epidermolytic palmoplantar keratoderma from Unna-Thost keratoderma. We report a case of hereditary epidermolytic palmoplantar keratoderma with literature reviews focused on the differential points from other palmoplantar keratodermas.

DNA-based Prenatal Diagnosis of Epidermolytic Palmoplantar Keratoderma in Two Pregnancies at Risk in One large Pedigree

BACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant disease of cornification which presents as severe thickening of the palms and soles with prominent epidermolytic hyperkeratosis pathologically. Recent studies have shown that EPPK is caused by mutations in the keratin 9 (K9) gene which is expressed essentially only in the palms and soles. Previously, We have reported that patients in one large pedigree of EPPK have an R162W substitution in the K9 protein. In this pedigree, two women whose husbands are both EPPK patients had become pregnant. OBJECTIVE: Since both women were concerned about this genetic disorder, we have performed prenatal diagnosis by biopsy analysis of chorionic villi tissue. METHODS: Chorionic villi biopsies were performed at 12 weeks gestation. Since the skin lesions are strictly confined to the palms and soles of the babies, the prenatal diagnosis of EPPK by ultrastructural analysis of fetal skin biopsy or amniotic fluid cells is highly problematic. Polymerase chain reaction amplification of specific allele (PASA) assay and direct DNA sequencing analyses were performed whether the fetuses carried mutant allele of K9 gene. RESULTS: PASA assay and direct DNA sequencing analyses showed that one fetus was normal, but the other fetus carried the abnormal allele. Subsequently, the mother of the unaffected fetus delivered a normal child, but the mother of the affected fetus terminated the pregnancy. CONCLUSION: We describe the analysis of the K9 mutation in the two fetuses at risk for EPPK. We believe that this is the first report of prenatal diagnosis for EPPK. But, we have to think about the ethical problems before we decide to perform the prenatal diagnosis of any kind of skin diseases.