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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.