PMC9619211_01
Brain MRI demonstrated diffuse, symmetrical abnormal signal in the bilateral cerebral white matter, which was low signal in T1WI (A), high signal in FLAIR (B), and high signal in T2WI (C).
fneur-13-1011019-g0001.jpg
PMC9619211_01_fneur-13-1011019-g0001.jpg
F1
Neuroradiologically, brain magnetic resonance imaging (MRI) scans demonstrated diffuse and symmetrical abnormal signals in the cerebral white matter, especially around the top of the lateral ventricle (Figure 1).
DNA sequencing. The patient (II-2) had compound heterozygous mutations of c.[185_186dupCA], p.(Asp63GlnfsTer18) and c.[154G>T], p.(Gly172Cys) in the ARSA gene. Her mother (I-2) and son (III-2) had the heterozygous mutation of c.[185_186dupCA], p.(Asp63GlnfsTer18). Her daughter (III-1) had the heterozygous mutation of c.154G>T, p.(Gly172Cys).
fneur-13-1011019-g0002.jpg
PMC9619211_01_fneur-13-1011019-g0002.jpg
F2
CA nucleotides located in exon 1 at c.185_186 resulted in a frameshift mutation (Figure 2). NM_000487: c.[154G>T], p.(Gly172Cys), rs74315271. A missense mutation of ARSA in exon 3 resulted in guanine being changed into thymine at nucleotide 154 (Figure 2), and amino acid Gly being replaced by Cys (Figures 3A,B). C.[185_186dupCA], p.(Asp63GlnfsTer18) was previously reported as a pathogenic mutation in the ARSA gene associated with MLD, but c.[154G>T], p.(Gly172Cys) was a novel mutation, which has not been reported in exome analysis. Family genetic analysis revealed that her mother and son were identified to carry the heterozygous mutation of c.[185_186dupCA], p.(Asp63GlnfsTer18), and her daughter was the carrier of the heterozygous mutation of c.[154G>T], p.(Gly172Cys) (Figure 2).
(A,B) Prediction of the three-dimensional structure of the protein. (A) The wild type of p.(Gly172Cys). (B) The mutated type of p.(Gly172Cys). The arrow indicates the mutation site. (C) Genetic family tree. A square represents a male, and a circle represents a female. A shaded symbol shows the proband, and a line across the symbol shows the deceased individual. A dot within the symbol represents carrier status for mutation c.[185_186dupCA], p.(Asp63GlnfsTer18). A triangle within the symbol represents carrier status for mutation c.[154G>T], p.(Gly172Cys).
fneur-13-1011019-g0003.jpg
PMC9619211_01_fneur-13-1011019-g0003.jpg
F3
CA nucleotides located in exon 1 at c.185_186 resulted in a frameshift mutation (Figure 2). NM_000487: c.[154G>T], p.(Gly172Cys), rs74315271. A missense mutation of ARSA in exon 3 resulted in guanine being changed into thymine at nucleotide 154 (Figure 2), and amino acid Gly being replaced by Cys (Figures 3A,B). C.[185_186dupCA], p.(Asp63GlnfsTer18) was previously reported as a pathogenic mutation in the ARSA gene associated with MLD, but c.[154G>T], p.(Gly172Cys) was a novel mutation, which has not been reported in exome analysis. The mode of inheritance of MLD is autosomal recessive, and a genetic family tree (Figure 3C) had been made.