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. Author manuscript; available in PMC: 2022 Jan 29.
Published in final edited form as: Neuron. 2020 Nov 20;109(2):241–256.e9. doi: 10.1016/j.neuron.2020.10.035

Figure 1. Biallelic mutations in PPIL1 lead to neurodegenerative pontocerebellar hypoplasia with microcephaly (PCHM) in human.

Figure 1.

(A) The families with predicted effects of PPIL1 variants listed above pedigree. All variants are homozygous in affected individuals, except Family 7–9, which are compound heterozygous. All pathogenic variants segregated as a recessive trait. Filled symbols: affected; p.[?]: splice donor site mutation, c.280+1G>A; square: male; circle: female; double bar: consanguinity; diagonal line: deceased. wt, reference allele; mut, patient variant allele.

(B) Sagittal (top) and axial (bottom) T1-weighted brain MRIs show reduced cerebellar volume (yellow arrowhead), atrophic pons (white arrowhead) and posterior fossa fluid accumulation (yellow arrows) indicative of cerebellar atrophy in affected individuals. Simplified gyri pattern is most apparent in the affected from Family 1 and 4.

(C) Identified PPIL1 mutations. Above: homozygous variants. Below: compound heterozygous mutations.

(D) En face view of enzymatic surface with labeled variant residues in NMR-resolved PPIL1 structure (PDB: 2K7N). All except R131 (blue) localized to the enzymatic surface. Red: duplicated region in Family 6 (A101-D106).

See also Figure S1.