De novo FTL mutation: A clinical, neuroimaging, and molecular study

A novel ferritin light chain mutation in neuroferritinopathy with an atypical presentation

“…This mutation is similar to the one presented here, with one nucleotide difference that causes a single amino acid change between both mutant ferritins at codon 162 (Fig. 5C); however, we have observed significant degree of variability in the presentation of the disease between the affected individuals from the Japanese family (tremor was the main characteristic symptom) (Ohta, 2008), the Italian patient (behavioral changes and tremor) (Storti, 2013) and our case. This difference may not be explained at the protein level, since the general structure of the spherical protein shell seems to be maintained in mutant ferritin as was seen by X-ray crystallography (Baraibar, 2010).…”

“…5B). As a result, the predicted mutant polypeptide (p.Leu162TrpfsX24) and the previously reported mutant polypeptide (p.Leu162ArgfsX24) (Ohta, 2008; Storti, 2013) have a different amino acid at codon 162 (tryptophan in p.Leu162TrpfsX24 and arginine in p.Leu162ArgfsX24) but identical sequence and length of the C-terminus of the mutant protein (Fig. 5C).…”

“…5B). The position of the mutation was near to that of previously reported Japanese (Ohta, 2008) and Italian (Storti, 2013) mutation, c.469_484dupGGCCCGGAGGCTGGGC, shifted one nucleotide to the 5′ of the previously reported mutation sequence. To confirm the presence of the mutation found in the proband, the PCR products of the amplification of exons 3 and 4 were subcloned and recombinant plasmid DNA isolated and sequenced in both directions.…”

“…Low serum ferritin levels were initially reported in individuals with the c.460InsA mutation (Curtis, 2001); however, low serum ferritin levels are not always observed in individuals with neuroferritinopathy (Curtis, 2001; Wills, 2002; Mancuso, 2005; Mir, 2005; Chinnery, 2007; Ohta, 2008; Ory-Magne, 2009; Devos, 2009; Ondo, 2010; Storti, 2013). Serum ferritin levels in our premenopausal female patient were 20 ng/mL (normal range, 5–204 ng/mL), and thus not found to be significantly decreased compared to normal range.…”

“…Patients carrying the mutation c.469_484dupGGCCCGGAGGCTGGGC have been described in Japan (Ohta, 2008) and Italy (Storti, 2013). This mutation is similar to the one presented here, with one nucleotide difference that causes a single amino acid change between both mutant ferritins at codon 162 (Fig.…”