Mutation analysis of the ADAR1 gene in dyschromatosis symmetrica hereditaria and genetic differentiation from both dyschromatosis universalis hereditaria and acropigmentatio reticularis.
Dyschromatosis symmetrica hereditaria (DSH) (also called "reticulate acropigmentation of Dohi") is a pigmentary genodermatosis of autosomal dominant inheritance. We have clarified for the first time four pathological mutations of the double-stranded RNA-specific adenosine deaminase gene (ADAR1 or DSRAD) in four DSH pedigrees. In this paper, we report 16 novel mutations containing six missense substitutions (p.V906F, p.K1003R, p.G1007R, p.C1036S, p.S1064F, p.R1078C), two splice site mutations (IVS2+2T>G, IVS8+2T>A), six frameshift mutations (p.H216fs, p.K433fs, p.G507fs, p.P727fs, p.V955fs, p.K1201fs), and two nonsense mutations (p.R426X, p.Q600X) found in Japanese patients with DSH. We did not establish any clear correlation between the clinical phenotypes and the genotypes of ADAR1 gene mutations in our examination of 16 cases plus four pedigrees. None of the different mutations identified in our studies of 20 cases suggested any founder effect. Furthermore, we did not identify any mutations in the ADAR1 gene of three patients with dyschromatosis universalis hereditaria or three patients with acropigmentatio reticularis, indicating that the two diseases are completely different from DSH, although they have sometimes been suggested to be phenotypical variations of DSH.
Suzuki
Noriyuki
N
Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Suzuki
Tamio
T
Inagaki
Katsuhiko
K
Ito
Shiro
S
Kono
Michihiro
M
Fukai
Kazuyoshi
K
Takama
Hiromichi
H
Sato
Kenji
K
Ishikawa
Osamu
O
Abe
Masatoshi
M
Shimizu
Hiroshi
H
Kawai
Masaaki
M
Horikawa
Tatsuya
T
Yoshida
Kunihiro
K
Matsumoto
Kazuhiko
K
Terui
Tadashi
T
Tsujioka
Kaoru
K
Tomita
Yasushi
Y
D000243:Adenosine Deaminase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D009154:Mutation; D010641:Phenotype; D010859:Pigmentation Disorders / Q000235:genetics* / Q000473:pathology; D011110:Polymorphism, Genetic; D016601:RNA-Binding Proteins
D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase