Four Novel Mutations Of The DSRAD Gene In Chinese Families With Dyschromatosis Symmetrica Hereditaria

Dyschromatosis symmetrica hereditaria (DSH),also called reticulate acropigmentation of Dohi.It is a pigmentary genodermatosis by the presence of hyperpigmented and hypopigmented macules on the dorsal aspects of the extremities and small freckle-like pigmented macules on the face.Onset is usually during infancy or early childhood,and commonly before adolescence.Histological studies shows that melanin pigmentation was increased in the basal cells of hyperpigmented lesions,but little melanin was found in hypopigmented macules.Generally,DSH shows an autosomal dominant pattern of inheritance with high penetrance.Zhang et al. have mapped the DSH gene on chromosome lqll-ql2.Pathogenic mutations were identified in the double-stranded RNA-specific adenosine deaminase (DSRAD) gene.Objective To identify mutations of DSRAD gene in four Chinese families with dyschromatosis symmetrica hereditaria.Method Blood samples were collected from the patients and healthy members of four families.The whole coding region of DSRAD gene was amplified by polymerase chain reaction (PCR) and PCR products were analyzed by direct sequencing.As control the DNA samples from 100 unrelated,normal adult individuals were also included.Results Four novel heterozygous mutations of DSRAD were identified in 4 Chinese families with DSH,which were c.3002G>T(p.R1001L) c.3089-3090delGA(p.R1030sX1036),c.3159delG(p.L1053fsâ†'1076X) and c.3209insC(p.L1070fsâ†'1092X).The missense mutation c.3002G>T(p.R1001L) in exon 11 of DSARD gene was identified in all patients from family A.The Gâ†'T mutation at nucleotide 3002 of DSRAD gene replaced a highly conserved arginine residue with leucine in codon 1001. And RT-PCR had been carried out to confirm this mutation.In family B we detected a novel frameshift mutation c.3089-3090delGA(p.R1030sX1036) in exon 12 of DSRAD gene.The two nucleotides. GA deleted at nucleotide from 3089 to 3090 results in frameshift and thus premature translation termination. A novel frameshift mutation in exon 12, c.3159delG(p.L1053fsâ†'1076X),of DSRAD gene was detected in the patients of family C.Another novel frame shift mutation, c.3209insC(p.L1070fsâ†'1092X), was detected in patients of family D.Conclusion These four mutations in the DSRAD gene have been detected in 4 DSH families,the novel mutations may be the causes of the clinical phenotype in these four families.