Association of human beta-defensin 1 gene polymorphisms with nonsegmental vitiligo.

BACKGROUND: Vitiligo is a pigmentation disorder of autoimmune aetiology. Polymorphisms in beta-defensin genes have been linked to a predisposition to some autoimmune disorders. AIM: To evaluate the role of polymorphisms in DEFB1, the gene encoding for human beta-defensin (HBD)-1 and its 5' untranslated region in nonsegmental vitiligo. METHODS: In total, 354 participants [171 patients with non-segmental vitiligo and 183 age and sex-matched healthy controls (HCs)], were genotyped by the PCR-restriction fragment length polymorphism (RFLP) method. For 80 of these individuals (40 patients and -40 HCs) serum HBD-1 was also measured by ELISA. RESULTS: The -44 G allele, CG genotype and GGG haplotype increased the risk for vitiligo (P < 0.02 in all cases), whereas the -20 AA genotype seems to be protective (P = 0.04). Serum HBD-1 levels were lower in patients with vitiligo than in HCs (P < 0.01), as well as in patients with active vitiligo compared with those with stable vitiligo and with HCs (P < 0.05 in both cases), CONCLUSION: Our results suggest that HBD-1 and its gene polymorphisms may modulate vitiligo susceptibility and/or disease activity. This is the first report, to our knowledge, of the association of serum HBD-1 levels and DEFB1 gene polymorphisms with vitiligo.

Pathogenic Compound Heterozygous Mutations in a Mexican Mestizo Patient with Niemann-Pick Disease Type B.

Niemann-Pick disease (NPD) type B is a lysosomal storage disorder caused by a deficiency of acid sphingomyelinase (ASM). We report the clinical follow-up of a 16-year-old Mexican mestizo woman with a NPD type B phenotype who presented hepatosplenomegaly, persitstenly low high-density lipoprotein (HDL) cholesterol and thrombocytopenia, without central nervous system involvement. After of a dengue fever episode with severe anemia and pancytopenia, leading to a bone marrow study n which foamy histiocytes were noticed and diagnosis of NiemannPick disease was suspected; and confirmed by biochemical and molecular tests. The missense c.1343 A>G (p.Tyr448Cys, formerly Y446C) and c. 1426C>T (p.Arg476Trp, formerly R474W) mutations in the SMPD1 gene were identified. These mutations have never been reported in the Mexican population. Since the c.1343 A>G (Y446C) mutation has been previously reported in a Japanese patient with NPD type A, we suggest an attenuator effect of c.1426C>T (R474W) allele (previously associated with the NPD type B phenotype). In conclusion, this is the first description of the concomitant occurrence of Y446C and R476W mutations in a Mexican patient with NPD type B, showing the importance of increased awareness and availability of specialized diagnostic tests in the diagnosis of rare inherited metabolic diseases.