HGM2002 Poster Abstracts: 8. Disease Mechanisms
POSTER NO: 429
Mutational analysis of ALD gene from a Chinese patient and his family with X-Linked Adrenoleukodystrophy
Fenghua Lan, Bosheng Yang, Yibo Wu, Yushui Wu, Qiaojia Huang
X-linked adrenoleukodystrophy (McKusick no. 300100; X-ALD) is a peroxisomal disease which mainly involves the white matter of central nervous system, the adrenal cortex and the testis. It is characterized by progressive demylination of the central nervous system and adrenal insufficiency. Although the clinical manifestations of the disease are highly heterogeneous, all patients with X-ALD have a similar accumulation of saturated very long chain fatty acids (VLCFAs) in plasma and somatic cells. The disease gene, the X-ALD gene, has been cloned and mapped to Xq28. It is 21 Kb in length, with 10 exons. It has been clarified that the X-ALD protein is a member of the ATP-binding cassette transporter superfamily located on the membrane of peroxisomes, but the definite function of the protein remains unclear. A 15 year-old male adolescent from Jiangxi Province, Southeastern China was referred to the Department of Neurology at our hospital and he was diagnosed X-ALD (adolescent cerebral type) according to his clinical phenotype, the results of magnetic resonance imaging (MRI) of his brain and elevated VLCFAs levels in the plasma. A sample of blood was drawn and total RNA was extracted. The X-ALD mRNA was analyzed by RT-PCR and direct squencing of PCR products. It was found that the patient has a point mutation at codon 280 of his X-ALD gene, changing Arg to Leu. This mutation was confirmed by Hin 6I restriction analysis of PCR-amplified genomic DNA sequence spanning the putative mutation. His family was also investigated and it was found that his mother and one of his two sisters were carriers of this mutation, but his younger brother was fortunately free of it. This is the first report on the molecular analysis of ALD gene in Chinese population.
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