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Homocysteine response to methionine challenge in four obligate heterozygotes for homocystinuria and relationship with cystathionine β ‐synthase mutations
Author(s) -
Sperandeo M. P.,
Candito M.,
Sebastio G.,
Rolland M. O.,
TurcCarel C.,
Giudicelli H.,
Dellamonica P.,
Andria G.
Publication year - 1996
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01799266
Subject(s) - homocystinuria , cystathionine beta synthase , homocysteine , methionine , mutation , allele , genetics , methionine synthase , biology , point mutation , heterozygote advantage , endocrinology , gene , medicine , amino acid
Summary Fasting and post‐methionine load plasma total homocysteine concentrations were investigated in the parents of two homocystinuric patients. Three genetic mutations in the cystathionine β ‐synthase gene were found. In the patient of family 1, a frequent Caucasian mutation, T 833 C, was found on one allele, while the mutation on the other allele has not yet been defined. In the patient of family 2, a mutation C 569 T, recently described by Sperandeo and colleagues, was found on one allele, while a novel mutation, G 346 A, was characterized on the other allele. The frequent gene mutation T 833 C was detected in a heterozygous mother who, surprisingly, exhibited strictly normal fasting and post‐methionine load homocysteinaemia. In contrast, in the other family, we found a novel mutation (G 346 A) in the mother located near Lys 119, the putative binding site of phosphopyridoxal phosphate. This mother exhibited increased fasting and post‐methionine load homocysteinaemia. These observations could explain the conflicting results reported for vascular pathologies in parents of homocystinuric patients and direct the search for genetic mutations in these vascular pathologies.