Two Novel Mutations Of The ADAR1Gene In Chinese Patients With Dyschromatosis Symmetrica Hereditaria

Background: Dyschromatosis symmetrica hereditaria (DSH)(also called ‘reticulateacropigmentation of Dohi’1or ‘symmetric dyschromatosisof the extremities’)(MIM127400) is characterized by a mixture of hyperpigmented and hypopigmented maculesand is localized on the back of the hands and feet. Many patients with DSH also havesmall freckle-like pigmented macules on their faces. The lesions usually appear ininfancy or early childhood, commonly stop spreading before adolescence, and last for life.Zhang et al. mapped the DSH locus to chromosome1q11–1q21, And then Miyamura et al.have clarified that a heterozygous mutation of the adenosine deaminase acting on RNA1(ADAR1, formerly DSRAD) gene causes DSH in4Japanese DSH families. So far, theremore than120mutations has been reported, including missense mutations, splicesitemutations, frameshift mutations, nonsense mutations. In this study, we investigated4sporadic cases that had no positive family histories from the Shandong Province of Chinato provide Genetic Counseling include gene diagnosis, prenatal diagnosis and genetherapy in the future.Objective: Here we performed genetic investigation in four sporadic cases that had nopositive family histories from the Shandong Province of China to detect the mutations inADAR1gene with DSH，To analyze the characteristic of the clinical feature andmutations in patients, and to investigate the relationship between the genotype andphenotype.Methods: Polymerase chain reaction(PCR) and direct sequencing of the ADAR1genewere performed to identify and confirm the mutations in the patients. Results: We identified two novel mutations (p.F535fs-563x, p.R544X) and onerecurrent missense mutation (p. R1155W) in the other two cases.None of these mutationswas found in100controls.Conclusion: By genetic investigation, three mutations were found in four unrelatedsporadic cases. And our findings contain two novle to the repertoire of ADAR1gene inDSH and provide a new data to the worldwide understanding of ADAR1genotype–phenotype correlation and to the pathogenesis of this disease.This study shouldbe useful for genetic counseling, prenatal diagnosis and gene therapy for the cases.