Kai-Lin Yan

Childhood psoriasis : a study of 277 patients from China

Objectives  Psoriasis is common in childhood. The aim of this study was to present the clinical and epidemiological profile of childhood psoriasis in China.

A Novel Linkage to Generalized Vitiligo on 4q13-q21 Identified in a Genomewide Linkage Analysis of Chinese Families

Generalized vitiligo is a common, autoimmune, familial-clustering depigmentary disorder of the skin and hair that results from selective destruction of melanocytes. Generalized vitiligo is likely a heterogeneous disease, with five susceptibility loci reported so far--on chromosomes 1p31, 6p21, 7q, 8p, and 17p13--in white populations. To investigate vitiligo susceptibility loci in the Chinese population, we performed a genomewide linkage analysis in 57 multiplex Chinese families, each with at least two affected siblings, and we identified interesting linkage evidence on 1p36, 4q13-q21, 6p21-p22, 6q24-q25, 14q12-q13, and 22q12. Subsequently, to extract more linkage information, we investigated our initial genomewide linkage findings in a follow-up analysis of 49 new families and additional markers. Our initial genomewide linkage analysis and our subsequent follow-up analysis have identified a novel linkage to vitiligo on 4q13-q21, with highly significant linkage evidence (a nonparametic LOD score of 4.62 [P=.000003] and a heterogeneity LOD score of 4.01, under a recessive inheritance model), suggesting that 4q13-q21 likely harbors a major susceptibility locus for vitiligo in the Chinese population. We observed a minimal overlap between the linkage results of our current genomewide analysis in the Chinese population and the results of previous analyses in white populations, and we thus hypothesize that, as a polygenic disorder, vitiligo may be associated with great genetic heterogeneity and a substantial difference in its genetic basis between ethnic populations.

The Epidemiology of Childhood Alopecia Areata in China: A Study of 226 Patients

Abstract:  To study the clinical and epidemiologic profile of childhood alopecia areata, we performed a survey in which a total of 226 childhood patients less than 16 years old were enrolled. Statistical analysis and heritability were performed using EPI INFO 6.0, SPSS10.0, and the Falconer method. The median age of onset was 10 years. The majority of patients (84.96%) presented with limited alopecia. The male : female ratio was 1.4:1. Boys appeared to have more severe involvement. The earlier the age of onset, the greater the severity of the disease. Sixty‐seven patients (29.65%) had previous episodes of alopecia areata. Greater severity and longer duration were seen in the relapsing patients than in the primary patients. Six patients (2.65%) had an associated disease. A positive family history was reported in 25 patients (11.06%). The prevalence figures for alopecia areata in first‐, second‐, and third‐degree relatives of the probands were 2.87%, 0.40%, and 0.13%, respectively. The heritabilities of AA in first‐, second‐, and third‐degree relatives were 51.20%, 46.25%, and 25.65%, respectively. It can be speculated that the effect of genetic factors is important in the occurrence of this disease.

Diverse phenotype of Brooke-Spiegler syndrome associated with a nonsense mutation in the CYLD tumor suppressor gene.

Abstract:  Brooke–Spiegler syndrome (BSS) is an autosomal dominant disease characterized by cylindromas, trichoepitheliomas and occasionally spiradenomas. The disease gene was mapped to 16q12‐13, and mutations in the CYLD gene were identified in families with BSS. In the present report, we describe a large consanguineous Chinese family with BSS showing an intra‐family phenotypic variability. Clinically, some affected individuals only revealed discrete small skin‐coloured tumors whereas the proband showed an expansion of multiple large tumors on the back of nose and numerous dome‐shaped papules on her scalp. Histologically, both trichoepitheliomas and cylindromas were found in the affected individuals. By sequence analysis, we identified a recurrent mutation 2272C>T (R758X) of the CYLD gene in the affected individuals of this family, which was previously identified in other ethnic families with familial cylindromatosis. Our result provided additional information for phenotype–genotype correlation in BSS.

Refined localization of a punctate palmoplantar keratoderma gene to a 5·06‐cM region at 15q22.2–15q22.31

Background  Punctate palmoplantar keratoderma (PPK) is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules distributed on the palms and soles. Two loci for punctate PPK were recently found to be located on 8q24.13–8q24.21 and 15q22–15q24. However, no genes for this disease have been identified to date.

A novel mutation of the DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria

Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. It is caused by mutations of the RNA‐specific adenosine deaminase gene. We report the identification of a Chinese family with a three‐generation pedigree of DSH, in whom a novel tyrosine substitution mutation in DSRAD was demonstrated: a heterozygous nucleotide A→G transition at position 2879 in exon 10 of the DSRAD gene was detected.

Refinement of a locus for Marie Unna hereditary hypotrichosis to a 1·1-cM interval at 8p21.3

Background  Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal congenital alopecia with progressive hair loss starting in early childhood and accelerating at puberty. A locus for MUHH has been mapped on chromosome 8p21 but no genes for MUHH have been identified to date.

Association of HLA-DQA1 and DQB1 alleles with alolpecia areata in Chinese Hans

Accumulative evidences have shown that certain HLA loci are associated with alopecia areata (AA), but with existing differences in ethnic distribution. No report has ever been published about this in Chinese Hans. To investigate whether HLA-DQA1 and DQB1 alleles are associated with AA, and the correlation of the HLA profile with age of onset, severity, duration of current attack, recurrence and family history of AA in Chinese Hans. The polymerase chain reaction–sequence-specific primer (PCR-SSP) method was used to analyze the distribution of HLA-DQA1 and DQB1 alleles in 192 patients with AA and 273 healthy controls in Chinese Hans. The significant increased frequencies of HLA-DQA1*0104 (OR=3.38, Pc<0.001), HLA-DQB1*0604 (OR=5.17, Pc=0.006) and HLA-DQA1*0606 (OR=3.73, Pc<0.001) were observed in patients compared with controls. The DQA1*0104-DQB1*0604, DQA1*0104-DQB1*0606, and DQA1*0302-DQB1*0606 were found as high-risk haplotypes in developing AA in this study. HLA-DQA1*0104 (OR=5.31, Pc < 0.001) and -DQB1*0604 (OR=5.56, Pc=0.015) were more prevalent only in AA patients with long duration than controls. The frequencies of HLA-DQB1*0604 (OR=5.42, Pc=0.009) and -DQB1*0606 (OR=4.11, Pc<0.001) were obviously increased in patients less than 50% scalp hair loss. No locus was merely associated with early onset, severe involvement, recurrence and a positive family history of AA. This study demonstrated the positive association of HLA-DQA1 and DQB1 alleles and haplotypes with AA. There may be differences in genetic background in patients with different duration.

Identification of a novel mutation in the DSRAD gene in a Chinese pedigree with dyschromatosis symmetrica hereditaria

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant skin disorder characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the face and dorsal aspects of the extremities that appear in infancy or early childhood. The DSH locus has recently been mapped to chromosome 1q21 and then pathogenic mutations have been identified in the DSRAD gene. In the study reported here we examined the DSRAD gene mutations of a three-generation Chinese pedigree with DSH by direct sequencing. We identified a novel heterozygous nucleotide T→C transition at position 3388 in exon 14 of the DSRAD gene which induces a C1130R change in the putative deaminase domain of DSRAD. Our study expands the database on the DSRAD gene mutations in DSH and enriches the knowledge about the function of the DSRAD gene.

Marie Unna hereditary hypotrichosis: report of a Chinese family and evidence for genetic heterogeneity.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant disorder with progressive hair loss starting in early childhood and aggravating at puberty. Several studies have mapped the MUHH gene to chromosome 8p21. Here we report a Chinese MUHH family with variable phenotypes. All affected individuals have anomalies affecting both hair density and hair shafts. Major clinical characteristics, disease history and histological examination support the diagnosis of MUHH, but the features of scarring in this kindred are modest and none of the patients have vertex hair loss, which is in contrast with typical MUHH. We now report genotyping and linkage analysis using 11 polymorphic microsatellite markers spanning the MUHH locus at 8p. Two‐point linkage analysis using these markers revealed significant exclusion of this locus (log of the odds scores < − 2) at θ = 0 indicating that there is a range of clinical presentations in MUHH, and that more than one genetic locus is responsible for the disorder.