LAUSR

To the Editor: We read with interest the article by Froese et al. [2016] reporting an exhaustively updated review on methylenetetrahydrofolatereductase (MTHFR, MIM# 607093) gene mutations. Among the 109 mutations from 192 patients described as causing severe MTHFR deficiency, the authors suggest that an inframe codon 215 deletion with consequent loss of a lysine at the protein level (c.643 645delAAG; p.Lys215del) can cause hyperhomocysteinemia, methylation alterations, and related diseases. This mutation was previously detected by the same investigators in a subject from 76 selected patients with clinical and biochemical evidence of MTHFR deficiency. However, in addition to the p.Lys215del, this patient carried a missense change (p.His127Tyr) on a FADbinding residue and the heterozygous c.677C>T (C677T) polymorphism [Burda et al., 2015], and showed brain atrophy and hydrocephalus by magnetic resonance imaging [Huemer et al., 2016]. The deletion was deposited as “Pathogenic” in the clinical variant database ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/;