S. Hazelwood et al., NORMAL BRAIN MYELINATION IN A PATIENT HOMOZYGOUS FOR A MUTATION THAT ENCODES A SEVERELY TRUNCATED METHIONINE ADENOSYLTRANSFERASE I III/, American journal of medical genetics, 75(4), 1998, pp. 395-400
Two isozymes of mammalian methionine adenosyltransferase, MAT I and MA
T III, are expressed solely in adult liver. They are, respectively, te
tramers and dimers of a single subunit encoded by the gene MAT1A. A th
ird isozyme, MAT II, contains a catalytic subunit encoded by a separat
e gene, MAT2A, and is expressed in a variety of tissues, including (to
a slight extent) adult liver. Based on a recent finding that 2 childr
en with isolated hypermethioninemia and brain demyelination were homoz
ygous for MAT1A mutations predicted to produce severely truncated prot
eins, and devoid of activity when expressed, it was concluded that com
plete lack of MAT I/III activity may be associated with neurological s
ymptoms and demyelination, We now report that a 43-year-old man with p
ersistent isolated hypermethioninemia, previously demonstrated to have
deficient MAT activity in his liver, has normal brain myelination on
MRI and normal neurological function, despite being homozygous for a 5
39 TG insertion in exon V of MAT1A, so that the gene is predicted to e
ncode a protein of only 184 rather than the normal 395 amino acids. Th
is patient's exon V mutation was demonstrated by SSCP analysis and ver
ified by sequencing, Both parents are heterozygous for the same insert
ion. This suggests that MAT1A mutations producing severely truncated p
roteins do not necessarily produce brain demyelination, This finding h
as relevance to a previously reported 4-year-old girl who was also hom
ozygous for the 539insTG mutation, Finally, our patient's 7% residual
hepatic MAT activity, measured at 1 mM methionine, may reflect the hep
atic activity of the more ubiquitous enzyme form. (C) 1998 Wiley-Liss,
Inc.(1)