OBJECTIVE: To detect variants of ADAR1 gene in two Chinese pedigrees affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: Clinical data and peripheral blood samples of the pedigrees were collected. All exons of the ADAR1 gene were amplified by PCR and subjected to Sanger sequencing. Suspected pathogenic variants were validated among other members of the pedigrees and 100 unrelated healthy controls. RESULTS: For pedigree 1, Sanger sequencing has identified a heterozygous missense variant c.3002G>C (p.Asp968His) in exon 11 of the ADAR1 gene in the proband and his father. For pedigree 2, a novel nonsense variant c.3145C>T (p.Gln1049Ter) was identified in exon 12 of the ADAR1 gene in the proband and his son, which were previously unreported and absent among the healthy controls. CONCLUSION The c.3002G>C (p.Asp968His) and c.3145C>T (p.Gln1049Ter)variants of the ADAR1 gene probably underlay the DSH in the two pedigrees.
Adenosine Deaminase/genetics* ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/genetics* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree. RESULTS: The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual. CONCLUSION The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.
Adenosine Deaminase/genetics* ; China ; Female ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To analyze the clinical features and genetic basis for a Chinese pedigree affected with hereditary dyschromatosis symmetrica hereditaria (DSH). METHODS: Peripheral blood samples of the proband and his mother were collected and subjected to PCR and Sanger sequencing. RESULTS: The patient has conformed to the typical pattern of DSH and manifested with hyperpigmentation, hypo- and hyperpigmentation spots on the back of hands, feet and face. Sanger sequencing confirmed that the proband and his mother have both harbored heterozygous splicing variant c.2762+1G>T in exon 9 of the ADAR gene, which was unreported previously. The same variant was not detected among 100 healthy controls. According to the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PM2+PP4). CONCLUSION The c.2762+1G>T variant of the ADAR gene probably underlay the DSH in this pedigree. Above finding has enriched the spectrum of ADAR gene mutations.
Adenosine Deaminase/genetics* ; China ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders/congenital* ; RNA-Binding Proteins/genetics*

OBJECTIVE: To detect mutations of ADAR gene in two pedigrees affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: Potential mutations of the ADAR gene were analyzed by Sanger sequencing of the probands from both pedigrees. Suspected mutations were validated by Sanger sequencing of other patients from both pedigrees as well as unrelated healthy individuals. RESULTS: A heterozygous nonsense mutation c.1325C>G (p.Ser442Ter) and a novel nonsense mutation c.1498C>T (p.Gln500Ter) were respectively identified in the ADAR gene among all patients from the two pedigrees but not among 200 healthy individuals. CONCLUSION Mutations of the ADAR gene probably underlie the DSH in the two pedigrees. Above findings have enriched the spectrum of ADAR gene mutation.
Adenosine Deaminase ; Humans ; Mutation ; Pedigree ; Pigmentation Disorders ; congenital ; genetics ; RNA-Binding Proteins

BACKGROUNDThe dyschromatoses are a group of disorders characterized by simultaneous hyperpigmented macules together with hypopigmented macules. Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria are two major types. While clinical and histological presentations are similar in these two diseases, genetic diagnosis is critical in the differential diagnosis of these entities.

METHODSThree patients initially diagnosed with DUH were included. The gene test was carried out by targeted gene sequencing. All mutations detected on ADAR1 and ABCB6 genes were analyzed according to the frequency in control database, the mutation types, and the published evidence to determine the pathogenicity.

RESULTSFamily pedigree and clinical presentations were reported in 3 patients from two Chinese families. All patients have prominent cutaneous dyschromatoses involving the whole body without systemic complications. Different pathogenic genes in these patients with similar phenotype were identified: One novel mutation on ADAR1 (c. 1325C>G) and one recurrent mutation in ABCB6 (c. 1270T>C), which successfully distinguished two diseases with the similar phenotype.

CONCLUSIONTargeted gene sequencing is an effective tool for genetic diagnosis in pigmentary skin diseases.

ATP-Binding Cassette Transporters ; genetics ; Adenosine Deaminase ; genetics ; Adolescent ; Asian Continental Ancestry Group ; Child ; Diagnosis, Differential ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Pedigree ; Pigmentation Disorders ; congenital ; diagnosis ; genetics ; RNA-Binding Proteins ; genetics ; Skin Diseases, Genetic ; diagnosis ; genetics

OBJECTIVETo analyse the mutation of ADAR gene in a pedigree with dyschromatosis symmetrical hereditaria (DSH).

METHODSA pedigree of DSH was investigated. Mutation scanning was carried out by PCR and direct sequencing. ADAR gene of 50 normal people was also sequenced as control. Through CBMdisc and PubMed, the mutations of ADAR gene were summarized.

RESULTSA novel mutation of c.2447G > A was found in all patients with DSH, but was not found in normal individuals in this DSH family and 50 unrelated controls. There were 64 mutations in ADAR gene.

CONCLUSIONA deletion mutation (c.2447G > A) in the ADAR gene has been detected in this DSH family, which is probably one of the molecular bases of the pathogenesis of the disease. Author have summarized a total of 64 mutations in the ADAR gene by previous reports and speculate that the mutation hotspots of ADAR gene might be located in the tRNA-specific and double-stranded RNA adenosine deaminase (ADEAMc) domain.

Adenosine Deaminase ; genetics ; Adult ; Base Sequence ; DNA Mutational Analysis ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Mutation ; Pedigree ; Pigmentation Disorders ; genetics ; Polymerase Chain Reaction ; RNA-Binding Proteins ; Skin Diseases, Genetic ; genetics

OBJECTIVETo identify potential mutation of the ADAR1 gene in a Chinese family and a sporadic case affected with dyschromatosis symmetrica hereditaria(DSH).

METHODSClinical data and peripheral blood samples from the pedigree and the sporadic patient were collected. Following extraction of genomic DNA, all 15 exons and exon-intron flanking sequences of the ADAR1 gene were amplified by polymerase chain reaction and subjected to direct sequencing.

RESULTSA novel frame-shift mutation c.2638delG (p.Asp880ThrfsX15) from the patients of the pedigree was detected in exon 8 of the ADAR1 gene. And a novel nonsense mutation c.2867C>A (p.Ser956X) was detected in exon 10 of the ADAR1 gene from the sporadic case. Neither mutation was identified among the unaffected family members nor 100 unrelated healthy controls.

CONCLUSIONThe frame-shift mutation c.2638delG (p.Asp880ThrfsX15) and the nonsense mutation c.2867C>A (p.Ser956X) in the ADAR1 gene probably underlie the DSH in our patients.

Adenosine Deaminase ; genetics ; Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; Codon, Nonsense ; Exons ; Female ; Frameshift Mutation ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Pigmentation Disorders ; congenital ; enzymology ; genetics ; RNA-Binding Proteins ; genetics

OBJECTIVETo detect mutation of ADAR1 gene in a family affected with dyschromatosis symmetrica hereditaria.

METHODSClinical data and blood samples of the family were collected. Potential mutation of the ADAR1 gene were scanned in 3 patients and 3 unaffected members by PCR amplification and direct sequencing. The coding sequences of the ADAR1 were also screened in 50 normal controls.

RESULTSA frameshift mutation (c.2252insG) of the ADAR1 gene was identified in all of the 3 patients. The same mutation was not found in the 3 unaffected members and 50 normal cases.

CONCLUSIONThe frameshift mutation of ADAR1 gene (c.2252insG) is probably responsible for the disease in this family.

Adenosine Deaminase ; genetics ; Adult ; Base Sequence ; Child ; China ; DNA Mutational Analysis ; Exons ; Female ; Frameshift Mutation ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Pigmentation Disorders ; congenital ; enzymology ; genetics ; Point Mutation ; RNA-Binding Proteins ; genetics

OBJECTIVETo analyze the mutation of the adenosine deaminase acting on RNA 1 (ADAR1) gene in a pedigree with dyschromatosis symmetrical hereditaria (DSH).

METHODSMutation analysis of the ADAR1 gene was carried out by PCR and direct DNA sequencing in the DSH family, as well as in 50 unrelated healthy controls.

RESULTSA missense mutation of c.3463C>T, which results in p.R1155W in the ADAR1 protein, was found in the 2 patients, but was absent in the 2 healthy members in the family and 50 unrelated individuals.

CONCLUSIONA missense mutation of c.3463C>T in the ADAR1 gene was detected in the DSH family, which is likely responsible for the pathogenesis of the disease.

Adenosine Deaminase ; genetics ; Amino Acid Sequence ; Base Sequence ; Child ; Child, Preschool ; Female ; Genotype ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Mutation, Missense ; Pedigree ; Pigmentation Disorders ; congenital ; enzymology ; genetics ; Point Mutation ; RNA-Binding Proteins ; Young Adult