Association between genetic variants in NOD2, C13orf31, and CCDC122 genes and leprosy among the Chinese Yi population.

BACKGROUND: A significant association between single nucleotide polymorphisms in NOD2, C13orf31, and CCDC122 genes and leprosy has been reported in a previous genome-wide association study of leprosy in the Chinese Han population. However, it remains unknown whether this association exists among the Chinese Yi population. The aim of this study was to investigate whether single nucleotide polymorphisms in NOD2, C13orf31, and CCDC122 genes are associated with leprosy among the Chinese Yi population in China. METHODS: We genotyped rs9302752, rs7194886, rs8057341, and rs3135499 in the NOD2 gene; rs3764147 and rs10507522 in the C13orf31 gene; and rs3088362 and rs9533634 in the CCDC122 gene in a Chinese Yi cohort comprised of 319 patients with leprosy and 355 ethnic-matched controls. The differences between the patients and healthy controls were analyzed using chi-squared analysis. RESULTS: Significant differences of rs3135499 in NOD2, rs3764147 and rs10507522 in C13orf31, and rs3088362 and rs9533634 in CCDC122 were observed between the patients and the healthy control groups in the cohort. The allelic P values and odd ratios were as follows: rs3135499, 1.0 × 10(-8) and 2.55; rs3764147, 1.7 × 10(-7) and 1.88; rs10507522, 1.16 × 10(-5) and 1.95; rs3088362, 8.2 × 10(-4) and 1.51; rs9533634, 5.34 × 10(-5) and 1.73. No significant differences were found in the distributions of rs9302752, rs7194886, and rs8057341 between the patients and healthy controls. CONCLUSIONS: We demonstrated that genetic variants in the NOD2, C13orf31, and CCDC122 genes are closely associated with leprosy among the Chinese Yi population, which implicates the pathogenic role of NOD2, C13orf31, and CCDC122 genes in a different ethnicity.

Two novel mutations on exon 8 and intron 65 of COL7A1 gene in two Chinese brothers result in recessive dystrophic epidermolysis bullosa.

Dystrophic epidermolysis bullosa is an inherited bullous dermatosis caused by the COL7A1 gene mutation in autosomal dominant or recessive mode. COL7A1 gene encodes type VII collagen - the main component of the anchoring fibrils at the dermal-epidermal junction. Besides the 730 mutations reported, we identified two novel COL7A1 gene mutations in a Chinese family, which caused recessive dystrophic epidermolysis bullosa (RDEB). The diagnosis was established histopathologically and ultrastructurally. After genomic DNA extraction from the peripheral blood sample of all subjects (5 pedigree members and 136 unrelated control individuals), COL7A1 gene screening was performed by polymerase chain reaction amplification and direct DNA sequencing of the whole coding exons and flanking intronic regions. Genetic analysis of the COL7A1 gene in affected individuals revealed compound heterozygotes with identical novel mutations. The maternal mutation is a 2-bp deletion at exon 8 (c.1006_1007delCA), leading to a subsequent reading frame-shift and producing a premature termination codon located 48 amino acids downstream in exon 9 (p.Q336EfsX48), consequently resulting in the truncation of 2561 amino acids downstream. This was only present in two affected brothers, but not in the other unaffected family members. The paternal mutation is a 1-bp deletion occurring at the first base of intron 65 (c.IVS5568+1delG) that deductively changes the strongly conserved GT dinucleotide at the 5' donor splice site, results in subsequent reading-through into intron 65, and creates a stop codon immediately following the amino acids encoded by exon 65 (GTAA→TAA). This is predicted to produce a truncated protein lacking of 1089 C-terminal amino acids downstream. The latter mutation was found in all family members except one of the two unaffected sisters. Both mutations were observed concurrently only in the two affected brothers. Neither mutation was discovered in 136 unrelated Chinese control individuals. This study reveals novel disease-causing mutations in the COL7A1 gene.