Figure 1. Identification of a missense variant in PDIA3 causing intellectual disability with developmental impairment.

1. Family pedigree. Filled symbols indicate subjects suffering from severe intellectual disability with developmental impairment, crossed symbols deceased subjects, horizontal lines subjects physically examined, * subjects who participated in genetic studies, and + subjects with SNP genotype data.
2. Pictures of affected individuals showing mild facial dysmorphism such as protruding ears and broad nose. From left to right, subjects 401, 502, and 504.
3. Palmar creases of subject 502. Distal and proximal creases indicated by black dashed lines are normal while thenar and median creases are missing.
4. Cranial MRI of subject 502 showing no gross structural brain defects.
5. DNA sequence electropherograms showing the substitution c.170G>A (p.Cys57Tyr) in PDIA3.
6. Domain structure of PDIA3. Catalytic (a and a′, with active site motif CGHC) and non‐catalytic (b and b′) domains are shown in green and blue, respectively. The C57Y mutant is depicted, with Y57 indicated by a red arrowhead. The region shown in gray corresponds to the X‐linker between domains b′ and a′.
7. Structural modeling of substitution of cysteine‐57 with tyrosine in the N‐terminal PDIA3 active site.