To the Editor:
Dyschromatosis symmetrica hereditaria (DSH)(Online Mendelian Inheritance in Man 127400), also called reticulate acropigmentation of Dohi, is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the dorsal aspects of the hands and feet. Linkage analysis has revealed that the DSH gene locus resides on chromosome 1q11-q21,1 and the adenosine deaminase RNA specific gene, ADAR1 (also called DSRAD), in this region has been identified as being responsible for the development of DSH.2 We report a sporadic case of severe DSH with the ADAR1 gene detected in a mutation analysis.
A 6-year-old girl presented with a mixture of hyperpigmented and hypopigmented macules on the dorsal aspects of the hands and feet and the curved side of the wrists, heels, and knees, as well as scattered frecklelike and depigmented spots on the face, ears, neck, arms, and upper back (Figure 1). Her parents noted that hyperpigmented and hypopigmented macules on the dorsal aspects of the hands developed at 5 months of age. Exacerbation after exposure to sunlight resulted in the eruption becoming remarkable in summer and fainter in winter. The skin lesions gradually became more progressive. Physical examination revealed that the patient generally was healthy.
Figure 1. A mixture of hyperpigmented and hypopigmented macules on the dorsal aspects of the hands (A), curved side of the wrists (B), knees, and dorsal aspects of the feet (C).
After obtaining informed consent, we performed a mutation analysis of the ADAR1 gene in our patient and her parents. We used a kit to extract genomic DNA from peripheral blood, which was then used to amplify the exons of the ADAR1 gene with intronic flanking sequences by polymerase chain reaction with the primer.3 After amplification, polymerase chain reaction products were purified. We sequenced the ADAR1 gene. Sequence comparisons and analysis found that the patient (proband) carried a heterozygous insertional mutation c.2253insG in exon 6 of the ADAR1 gene. This mutation was not detected in the proband’s healthy parents and 100 normal individuals (Figure 2).
Figure 2. Identification of the ADAR1 (adenosine deaminase RNA specific) gene mutation with a heterozygous insertion mutation c.2253insG in exon 6 (A) and wild-type allele in a normal control in exon 6 (B).
Dyschromatosis symmetrica hereditaria is acquired by autosomal-dominant inheritance and is mainly reported in Asians, especially in Japan and China. Oyama et al4 reviewed 185 cases of DSH in Japan and found the onset of this disease usually was during infancy or childhood; 73% of patients developed the skin lesions before 6 years of age. Suzuki et al5 reported 10 unrelated Japanese patients and found the onset of disease ranged from 1 year of age to childhood. Zhang et al1,6 investigated 78 Chinese patients with DSH including 8 multigenerational families and 2 sporadic patients and found the age of disease onset ranged from 6 months to 15 years of age. The age of onset in our patient (5 months) was younger than these prior reports.