Analysis Of A Pedigree With Dyschromatosis Symmetrica Hereditaria

BackgroundDyschromatosis symmetrica hereditaria (DSH, OMIM 127400), also called reticulate acropigmentation of Dohi, is a rare autosomal dominant pigmentary genodermatosis. DSH was first described by Toyama in 1910, and named later in 1929, which is characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes mostly on the dorsal aspects of the extremities. On the face, the lesions resemble ephelides and no hypopigmentation appears. These abnormalities are otherwise asymptomatic and do not affect the general health of the patient. Miyamura et al. confirmed that the ADAR gene which is located in lq21.3 spanning 500kb regions is responsible for DSH in 2003. Dyschromatosis universalis hereditaria (DUH OMIM 127500) is a rare autosomal dominant inherited disease characterized by generalized hyper-and hypo-pigmentation of the skin. Early studies suggested that DSH might be a subtype of this disease. However, recent studies on pathogenic genes have revealed that DSH and DUH belong to two distinct disease entities. Reticulate pigmented anomaly of the flexures (RPAF, OMIM 179850), also called Dowling-Degos disease (DDD), is a new identifined and rare genodermatosis, which shows an autosomal dominant pattern of inheritance which is characterized by spotted and reticulate pigmentation of the flexures, including flexural areas of wrist, antecubital fossae, axillae, lower abdomen, the groin and popliteal fossae. DSH has many similarities with DUH and DDD in clinical manifestations and pathological features. Genomic methods are the best way to differentiate. Objective1,To detect the mutations in ADAR gene of patients.2,To detect mutation of the suspected patient with atypical clinical features with the aim of making diagnosis.Methods1,Analyze the information of family and summarize the characteristics.2,Polymerase chain reaction (PCR) amplification of the ADAR gene was performed spanning all 15 exons and flanking sequence of ADAR gene and direct sequencing was performed to screen the mutations in ADAR gene.3,Design STR markers of DSH, DUH, DDD and perform linkage analysis of the family.Result1,Clinical manifestation shows obvious remission by the changes from typical presentation to freckle-like maculae localized only on the face following the generations. Besides, we found a novel manifestation of dyschromatosis in lip.2,No mutations were identified by direct sequencing of all 15 exons and flanking sequence.3,6q24.2-q25.2,12q21-q2,12q13were excluded by linkage analysis. For the STR marker (chrl:154528835-154528881,1q22) of DSH, when recombinant frequencyθ=0, Lod=3.01, linkage was confirmed.Conclusion1,By analyzing the information of family, we summarize the relationship of clinical manifestation and generations. Also we found a novel manifestation.2,Linkage was confirmed in the position that 5000kb nearby ADAR.3,We excluded the possibilities of DSH for the suspected patient. 4,As no mutations were found in all 15 exons and flanking sequence, we presumed the causal gene may be located in intron regions, promoter regions of 5'or other gene nearby ADAR. Studies need to be continued.