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Determination of 30 X‐linked adrenoleukodystrophy mutations, including 15 not previously described
Author(s) -
Lachtermacher M.B.R.,
Seuánez H.N.,
Moser A.B.,
Moser H.W.,
Smith K.D.
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(200004)15:4<348::aid-humu7>3.0.co;2-n
Subject(s) - adrenoleukodystrophy , biology , peroxisome , mutation , peroxisomal disorder , leukodystrophy , genetics , phenotype , gene , medicine , disease
X‐linked Adrenoleukodystrophy (X‐ALD) is the most frequent peroxisomal disease. It mainly involves the nervous system white matter, adrenal cortex and testes. Several distinct clinical phenotypes are known. The principal biochemical abnormality is the accumulation of saturated very‐long‐chain fatty acids (VLCFAs : > C22:0, mainly C26:0), which is due to impaired capacity for β‐oxidation in peroxisomes. Diagnosis is usually based on the VLCFA levels in plasma or cultured skin fibroblasts in both patients and carriers. In 0.1% of affected males, however, the plasma C26:0 level is borderline normal, and 15% of obligate female carriers have normal results. Effective mutation detection in these families is therefore fundamental to unambiguously determine the genetic status of each individual at risk. Of particular concern are female members of kindreds segregating X‐ALD mutations, because normal VLCFA levels do not guarantee lack of carrier status. We describe a fast method for detection of X‐ALD mutations. The method is based on SSCP analysis of nested PCR fragments followed by sequence‐determination reactions. Using this methodology we have found X‐ALD mutations in 30 kindreds, including 15 not previously reported. Hum Mutat 15:348–353, 2000. © 2000 Wiley‐Liss, Inc.