Identification of a novel splicing mutation in the ARSA gene in a patient with late-infantile form of metachromatic leukodystrophy.
Metachromatic leukodystrophy (MLD; MIM 250100), a severe neurodegenerative disorder inherited as an autosomal recessive trait, is caused by mutations in the arylsulfatase A (ARSA) gene. Although several germ line ARSA mutations have been identified in patients with MLD of various ethnic backgrounds elsewhere in the world, no genetically confirmed cases of MLD have been reported in Korea. Recently, we identified a mutation in the ARSA gene of a Korean male with MLD. A male infant with late-infantile form of MLD had been admitted to our hospital for further examination. His neuromuscular symptoms, which included inability to walk at the age of 12 months, gradually worsened, even after allograft bone marrow transplantation; he died at the age of 9 yr. His elder brother had also been diagnosed with MLD. To confirm the presence of a genetic abnormality, all the coding exons of the ARSA gene and the flanking introns were amplified by PCR. A molecular analysis of the ARSA gene revealed both a novel heterozygous splicing mutation (c.1101+1G>T) in intron 6 and a heterozygous missense mutation in exon 2 (c.296G>A; Gly99Asp). The patient's elder brother who had MLD is believed to have had the same mutation, which may be correlated with a rapidly deteriorating clinical course. This study identified a novel mutation in the ARSA gene, related to a late-infantile form of MLD with a lethal clinical course and suggested that molecular diagnosis of patients may be useful in early diagnosis and for deciding intervention measures for their family members.
Kang
Dong-Hee
DH
Department of Laboratory Medicine and Genetics, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.
Lee
Dong Hwan
DH
Hong
Yong-Hee
YH
Lee
Seung-Tae
ST
Jeon
Byung Ryul
BR
Lee
You Kyoung
YK
Ki
Chang-Seok
CS
Lee
Yong-Wha
YW
D002553:Cerebroside-Sulfatase / Q000235:genetics*; D005091:Exons; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007438:Introns; D007966:Leukodystrophy, Metachromatic / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D002553:Cerebroside-Sulfatase