Disruption of Intracellular Calcium Homeostasis Leads to ERLIN2-Linked Hereditary Spastic Paraplegia in Patient-Derived Stem Cell Models

Figure 1

Identification of ERLIN2 heterozygous missense variants in the hereditary spastic paraplegia (HSP) family and molecular characterization. (a) Pedigrees of HSP families. Shaded symbols are affected with features of HSP, white symbols are normal, and a plus sign and a minus sign mean the heterozygous variant of ERLIN2 missense variant c.212T>C: p.Val71Ala. (b) Clinical features of individual II-2 and II-5, such as amyostasia, amyotrophy, and myospasm. (c) The partial nucleotide sequences of exon 4 of ERLIN2 show the c.212T>C: p.Val71Ala variant in the affected family members (II-2, II-3, II-5, III-1, and III-3) and the normal control. (d) Multiple sequence alignment of the ERLIN2 partial region. The arrow indicates the amino acid position 71 in human ERLIN2. (e) The ERLIN2 protein consists of three main domains, the SPFH domain (residues 22–226), the oligomerization domain (residues 228–300), and a short hydrophobic patch (residue at position 305). The c.212T>C: p.V71A variant is located in the SPFH domain, and the asterisk indicates the variant originated from our patient.

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