36. Biochemical and molecular findings in a LIMP-2 deficient patient who presented with myoclonic epilepsy and no signs of renal involvement

Abstract

Previous studies have shown conflicting findings in linking polymorphic variation in folate-related genes to the risk of neural tube defect pregnancy. Recent evidence points to maternal genotype being important in determining NTD risk. A case-control study was undertaken in 97 mothers of NTD cases from the northern region of the UK. Pregnant controls (n=190) from a regional DNA bank and non-pregnant controls (n=100) from the same geographical area were recruited. MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, SHMT 1420C>T, CβS 844ins68, and RFC-1 80G>A allele and genotype frequencies were determined and odds ratios (OR) calculated. Erythrocyte folate levels for cases and controls were also measured and a comparison made of median erythrocyte folate levels stratified according to genotype. The MTHFR 677C>T variant was not shown to be an independent NTD risk factor in mothers of NTD-affected pregnancy. A second polymorphism in MTHFR, 1298A>C, was less frequently observed in mothers of NTD cases (OR [95% CI]=0.57 [0.33, 0.97]). Possession of compound 1298A>C and 677C>T variants elevated risk of NTD pregnancy considerably (TT/AC + TT/CC vs CC/AA OR [95% CI]=6.56 [1.10, 39.33]). Erythrocyte folate levels were persistently lower in NTD mothers (p=0.001) despite assays being conducted many years after the index pregnancy (17.6 ± 12.6 years). Erythrocyte folate levels were depressed in the presence of the MTHFR 677C>T variant.