[Novel missense mutations of the FLG gene identified in two Chinese families affected with ichthyosis vulgaris].

OBJECTIVE: To identify potential mutations of the FLG gene in two Chinese families affected with ichthyosis vulgaris. METHODS: All coding exons and exon-intron boundary of the FLG gene were amplified by polymerase chain reaction (PCR) and analyzed by direct sequencing. The results were compared with those of 100 unrelated healthy controls. RESULTS: Two novel missense mutations, c.1360A>G (p.T454A) and c.10363G>T (p.D3455Y), were detected in all affected individuals from family 1 and family 2 respectively but none of the controls. CONCLUSION: The c.1360A>G (p.T454A) and c.10363G>T (p.D3455Y) of the FLG gene may lead to alteration of the structure and function of the FLG protein and cause ichthyosis vulgaris in the two families.

Analysis of Taiwanese ichthyosis vulgaris families further demonstrates differences in FLG mutations between European and Asian populations.

BACKGROUND: Mutations in the gene encoding filaggrin (FLG) were identified to underlie ichthyosis vulgaris (IV) and also shown to predispose to atopic eczema. Until now, no FLG mutations have been described in the Taiwanese population. OBJECTIVES: To elucidate filaggrin mutations in the Taiwanese population and further to clarify the population genetics of filaggrin gene mutations in the Asian populations. METHODS: In the present study, 12 individuals from four unrelated Taiwanese IV families were examined for FLG mutations. We carried out comprehensive sequencing of the entire FLG coding region using an overlapping polymerase chain reaction strategy. RESULTS: We identified three FLG mutations in the Taiwanese IV families. One mutation E1795X was a previously unidentified FLG mutation, which might be specific to the Taiwanese. Interestingly, another FLG mutation 3321delA is prevalent in the Japanese population and the other mutation Q2417X was found in the Singaporean Chinese population. No FLG mutation identified in the white European population was found in the Taiwanese population. CONCLUSIONS: The present findings suggest that the Taiwanese population, as an East Asian group, share FLG mutations with both the Japanese and the Singaporean Chinese population. In addition, these results exemplify differences in the population genetics of filaggrin between Europe and Asia.

Specific filaggrin mutations cause ichthyosis vulgaris and are significantly associated with atopic dermatitis in Japan.

Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and shown to be major predisposing factors for atopic dermatitis (AD). However, these studies have been mainly carried out in European populations. In early 2007, we identified two Oriental-specific FLG mutations in four Japanese families with IV and reported that filaggrin mutations were also significant predisposing factors for AD in Japan. However, the frequency of FLG mutations observed in our Japanese AD cohort (5.6%), was much lower than that seen in Europeans (up to 48%). Here, we studied a further seven Japanese families with IV and identified two additional nonsense mutations in FLG, S2889X, and S3296X. We found that more than 20% of patients in our Japanese AD case series carry FLG mutations, and there is significant statistical association between the four mutations and AD (chi(2) P=8.4 x 10(-6); heterozygote odds ratio 7.57, 95% CI 2.84-23.03). These data emphasize that skin-barrier impairment due to reduced filaggrin expression plays an important role in the pathogenesis of AD and sheds further light on the genetic architecture of atopy in Japan.

Identification of a genetic locus for ichthyosis vulgaris on chromosome 10q22.3-q24.2.

Ichthyosis vulgaris (IV) is one of the most commonly inherited disorders and has an estimated prevalence rate of 2.29% in China. To date, only one gene responsible for IV, the filaggrin gene (FLG), was identified, but genetic heterogeneity exists. In this study, two Chinese families with autosomal-dominant IV were genetically characterized. The FLG gene was first excluded as the disease-causing gene in the two families. The larger family was then characterized by genome-wide linkage analysis to identify a new genetic locus for IV. Significant linkage was identified with markers on chromosome 10q22.3-q24.2 with a maximum LOD score of 3.19. No other markers showed a LOD score of >1.5. Fine mapping defined the new genetic locus within a 20.7 cM region between markers D10S569 and D10S1709. The second family also showed positive linkage to the same 10q22.3-q24.2 region. The combined maximum LOD score in the two families was 3.95. Identification of linkage in two independent families provides strong genetic evidence that a previously unreported gene for IV is located on chromosome 10q22.3-q24.2. Future studies of the candidate genes at the 10q IV locus will identify a specific gene, which will provide insights into the pathogenesis of IV.

Clinico-epidemiological profile of ichthyosis in south Indian patients.

A high frequency rate of hereditary ichthyosis (141.89 per 1000) was detected in a 1029 member South Indian study population selected at random from the skin outpatients of a teaching hospital. An age and sex matched control population screened from the medical and pediatric outpatients of the same institute recorded the incidence of ichthyosis vulgaris as 150 per 1000 population which is even higher.