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Figure 1. Pedigree and molecular findings of family A. A: There are two
affected siblings (IV-2 and IV-3) with clinical features of complicated
hereditary spastic paraplegia, indicated with blue color. Proband’s
father, aunt and uncles (III-1,2,3) represented with Griscelli
appearance, green color. C: The nucleotide and amino acid sequences in
the mutation site (c.1568delC, p.S523Ffs*12) are shown. In normal
protein, TCT codon codes serin residue at 523th amino acid, while
c.1568delC changes this amino acid to phenylalanine and creates
premature stop codon exactly 11 amino acids after mutated residue,
causing truncated protein. B and D illustrate nucleotide sequences inTECPR2 and MLPH respectively. Mother is carrier for both
mutations, while the affected sibling is homozygote for identified
alterations. In addition, the mutation in TECPR2 gene was not found in
the healthy elder sibling, however, the mutation in MLPH gene was
identified in heterozygote manner.
Figure 2. Pedigree and molecular findings of family B. A: MRI imaging at
age 5 which shows very mild abnormal deep white matter periventricular
(yellow arrows). B: Pedigree of the family. The proband has been
indicated by the arrow. C: The mutation segregation by Sanger sequencing
has been done for the proband’s relatives. As can be seen in sequence
chromatograms, his parents (III-3 and III-4) are heterozygotes for c.
del685-687 and the proband (IV-1, colored in red) is homozygous. D: The
deletion of three nucleotides leads to non-frameshift deletion of highly
conserved amino acid Isoleucine at 229th residue as shown by the
orthologous sequences (https://blast.ncbi.nlm.nih.gov/Blast.cgi). E:
Schematic representation of 7 exons of the FA2H and its two highly
conserved domains; cytochrome b5-like heme-binding domain (residues
15–85) and sterol desaturase domain (residues 124-366). The identified
variant in this study was shown.