X-linked adrenoleukodystrophy (X-ALD) is a congenital peroxysomal disorder caused by mutations in the ALD protein gene (ALD or ABCD1) located to Xq28 [Mosser et al., 1993]. Its phenotype is variable, ranging from the severe childhood cerebral form that is associated with rapidly progressive demyelinating as an inflammatory response in the cerebral white matter, to the adult form of slowly progressive adrenomyeloneuropathy (AMN), and Addison disease only . Biochemical abnormality of the disorder is an accumulation of very long chain fatty acid (VLCFA). The diagnosis of X-ALD is based on clinical manifestations, including neurological signs and symptoms, serum VLCFA levels, brain MRI findings, and hormonal data, as well as on mutation analysis of ALD. Serum VLCFA levels are sometimes in the normal range in heterozygous women . As large genomic rearrangements are infrequent, nucleotide sequence analysis is diagnostic for most pedigrees, especially for carrier diagnosis . More than 300 different mutations in ALD have been identified and registered in a database (http://www.x-ald.nl/). Among point mutations reported, base substitutions were most frequent and distributed over the gene. There is no difference in frequency of ALD mutations among different ethnic populations , or no genotype-phenotype correlation, suggesting the presence of factor(s) modifying the phenotype .
The plexin B3 gene (PLXNB3) is located 20.4-kb apart in the 3 0 direction from ALD. The mouse plexin b3 (Plxnb3), a functional receptor for semaphorin , was reported to be expressed mainly in the brain and the dorsal root ganglia postnatally, and supposed to be related to the differentiation and migration of oligodendrocytes . There have been no reports of human plexin B3 deficiency. Here we report a case of ALD with a partial deletion of the ALD and PLXNB3 genes.
The proband, a 3-year-old boy, was referred to us for molecular diagnosis of his ALD. There were no other ALD/ AMN patients in his family. He was born at 40 weeks gestation with a birth weight of 3,198 g. His developmental milestones