Four novel mutations of ADAR1 in Chinese patients with dyschromatosis symmetrica hereditaria.

BACKGROUND: Novel mutations in adenosine deaminase acting on RNA 1 gene (ADAR1) are responsible for dyschromatosis symmetrica hereditaria (DSH). DSH patients display a mixture of hyperpigmented and hypopigmented macules on the dorsal aspects of the extremities, and freckle-like macules on the face. AIMS: To provide new evidence for further study of the etiopathogenisis of DSH. METHODS: Genomic DNA was extracted and used as a template for the polymerase chain reaction (PCR) amplification of all 15 coding exons as well as intron-exon boundaries of ADAR1. The PCR products were sequenced directly. RESULTS: We identified eight mutations of ADAR1 in four Chinese pedigrees and four individual patients, which were c.2722G>T, p.(Asp908Tyr), c.1657delA, p.(Ser553fs), c.2563_2564delCT, p.(Leu855fs), c.526T>G, p.(Leu176Val) as well as four previously reported mutations c. 3363_3364insT, p.(Lys1122fs), c. 2865_2866delGT, p.(Val955fs), c.1630C>T, p.(Arg544X), and c.2894C>T, p.(Pro965Leu). In silico analysis predicted that all the mutations reported were pathogenic. LIMITATIONS: We did not study how ADAR1 played its role in DSH. So, the exact pathogenic mechanism of ADAR1 in DSH patients wasn't clarified in this study. CONCLUSION: We found four novel ADAR1 mutations in this study. Our results enlarge the database on ADAR1 mutations associated with DSH.

Mongolian spots.

Mongolian spots (MS) are birthmarks that are present at birth and their most common location is sacrococcygeal or lumbar area. Lesions may be single or multiple and usually involve < 5% total body surface area. They are macular and round, oval or irregular in shape. The color varies from blue to greenish, gray, black or a combination of any of the above. The size varies from few to more than 20 centimetres. Pigmentation is most intense at the age of one year and gradually fades thereafter. It is rarely seen after the age of 6 years. Aberrant MS over occiput, temple, mandibular area, shoulders and limbs may be confused with other dermal melanocytoses and bruises secondary to child abuse, thus necessitating documentation at birth. Although regarded as benign, recent data suggest that MS may be associated with inborn errors of metabolism and neurocristopathies. Mongolian spots usually resolve by early childhood and hence no treatment is generally needed if they are located in the sacral area. However, sometimes it may be required for extrasacral lesions for cosmesis.

Nail dyschromias.

Nail dyschromias have a wide variety of presentation. There are numerous causes of discoloration of the nail affecting the nail plate, nail attachments, or the substance of the nail. The chromonychia may also be caused due to the exogenous deposition of pigments over the nail plate. Careful examination of the nail and few bed side tests may help in identifying the root cause of the nail dyschromia and many a times unravels some underlying systemic disorder too.

Three cases of Dowling Degos disease in two families.

Dowling Degos disease is a rare condition inherited as autosomal dominant trait characterized by numerous, asymptomatic, symmetrical, progressive, small, round-pigmented macules over axillae and groins, face, neck, arms and trunk, scattered comedo-like lesions (dark dot follicles) and pitted acneiform scars. Histopathology is diagnostic. We are hereby reporting three cases of Dowling Degos disease belonging to two families. Our first and second case belonged to the same family, whereas our third case belonged to different family. In our series, all the patients had onset after puberty. All three cases had reticulate pigmentation over face and/or flexures, black comedones and follicular pits. On histopathological examination of the skin biopsy taken from the lesion over the back, all these patients showed classical histopathological features of Dowling Degos disease. We feel that one should investigate the patient presenting with reticulate pigmentation over the face and flexures with blackish comedone-like lesions, because histopathological features of this condition are unmistakable.