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PYCR1 – Geroderma Osteodysplasticum

PYCR1 encodes mitochondrial pyrroline-5-carboxylate reductase 1 and is implicated in autosomal recessive geroderma osteodysplasticum. In a consanguineous family, four affected siblings presented with dorsum-limited skin wrinkling, osteopenia, mandibular prognathism, and severe intellectual disability and were homozygous for a PYCR1 variant (c.356G>A (p.Arg119His)) ([PMID:21204221]). Functional assays of the p.Arg119His mutant demonstrated a temperature-sensitive decrease in protein stability and catalytic efficiency, with near-abolished activity at 37 °C, consistent with a loss-of-function mechanism ([PMID:28194412]). No conflicting reports have been described.

References

  • American journal of medical genetics. Part A • 2011 • The phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than autosomal recessive cutis laxa type 2 PMID:21204221
  • BioMed research international • 2017 • Effect of R119G Mutation on Human P5CR1 Dynamic Property and Enzymatic Activity PMID:28194412

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

4 probands in one consanguineous family with phenotypic concordance ([PMID:21204221])

Genetic Evidence

Limited

Homozygous PYCR1 variant identified in four affected individuals in a single family ([PMID:21204221])

Functional Evidence

Moderate

In vitro assays show temperature-sensitive loss of enzymatic function for p.Arg119His variant ([PMID:28194412])