OBJECTIVE: To explore the genetic basis for a Chinese patient suspected for Canavan disease. METHODS: Whole exome sequencing (WES) was carried out for the proband, and candidate variants were verified by Sanger sequencing of the proband, her parents and brother. Prenatal diagnosis was provided to her mother by chorionic villi sampling (CVS) upon her subsequent pregnancy. RESULTS: The proband, a 4-month-old female infant, had manifested drowsiness, hypotonia and apathy. Urine metabolism screening showed elevated N-acetylaspartic acid. Cranial magnetic resonance imaging revealed abnormal myelination and multiple abnormal signals in large brain areas. WES revealed that the proband has harbored compound heterozygous variants of the ASPA gene, namely c.187A>G (p.Arg63Gly) in exon 1 and c.634+1G>A (P.?) in exon 4. Sanger sequencing confirmed that the c.187A>G (p.Arg63Gly) and c.634+1G>A (p.?) variants were respectively inherited from her mother and father. Her phenotypically normal brother has carried a heterozygous c.634+1G>A (p.?) variant. Prenatal diagnosis by CVS indicated that the fetus was a heterozygous carrier of the c.187A>G variant. CONCLUSION WES can facilitate the diagnosis of Canavan disease, particularly for those lacking specific phenotypes of the disease. The compound heterozygous variants of the ASPA gene probably underlay the Canavan disease in this patient, and the result has enabled prenatal diagnosis for this family.
Canavan Disease/genetics* ; China ; Female ; Humans ; Male ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo elucidate the relation between cytochrome P4502D6 (CYP2D6) gene polymorphism and the susceptibility of heroin spongiform leucoencephalopathy (HSLE).

METHODSWith polymerase chain reaction-restriction fragment length polymorphism technique, the cytochrome P4502D6 gene polymorphisms were analyzed in HSLE cases and control subjects.

RESULTSThe frequencies of CYP2D6 (CYP2D6/C188, CYP2D6/L2938, CYP2D6/G4268) gene mutations were higher in HSLE patients than in the controls.

CONCLUSIONThe CYP2D6 gene mutation is associated with a high risk of HSLE.

Adult ; Canavan Disease ; chemically induced ; genetics ; Cytochrome P-450 CYP2D6 ; genetics ; Female ; Heroin ; adverse effects ; Heroin Dependence ; complications ; Humans ; Male ; Middle Aged ; Mutation ; Polymorphism, Restriction Fragment Length ; Young Adult