[Analysis of ARSA mutations in a Chinese family with metachromatic leukodystrophy].
OBJECTIVE
To identify arylsulftase A gene (ARSA) mutations in a Chinese family with MLD.


METHODS
There were two MLD patients in the investigated family. The proband, an 11-year-old girl, was well until the age of 5 years, when she began to experience difficult walking and mental regression. Magnetic resonance imaging (MRI) of her brain showed widespread demyelination, nerve conduction velocity reduced, and ASA activity measured in white blood cells was zero. So, the child was diagnosed having MLD. The proband's young brother also got the same phenotype except clinical symptom being milder than hers. Their parents and elder sister all had normal phenotypes. Genomic DNA samples were extracted from peripheral bloods of the proband and all her family members. All 8 exons and exon-intron boundaries of ARSA gene were amplified by polymerase chain reaction (PCR) and followed by direct DNA sequencing.


RESULTS
Two heterozygous mutations of ARSA, which were named as, G251A (R84Q) and G296T (G99V) were identified in the proband. The two mutations were located in exon 2. The same genotype was found in the proband's young brother, but these mutations were not detected in proband's elder sister. The proband's mother had the heterozygous mutations G296T (G99V), and her father had the heterozygous mutation G251A (R84Q).


CONCLUSIONS
These two MLD patients are with both compound heterozygous mutations, which mean one allele with the G296T (G99V) mutation was from their mother, and the other allele with the G251A (R84Q) mutation got from their father. The parents are both carrier with normal phenotype.
Wang
Jing-min
JM
Department of Pediatrics, First Hospital, Peking University, Beijing 100034, P. R. China.
Jiang
Yu-wu
YW
Shi
Hui-ping
HP
Zhang
Wei-min
WM
Pan
Hong
H
Bao
Xin-hua
XH
Wu
Ye
Y
Qin
Jiong
J
Wu
Xi-ru
XR
D000483:Alleles; D001483:Base Sequence; D002553:Cerebroside-Sulfatase / Q000235:genetics*; D002648:Child; D002681:China; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007966:Leukodystrophy, Metachromatic / Q000235:genetics* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010375:Pedigree
D002553:Cerebroside-Sulfatase