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Updated: Aug 4, 2025
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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
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Biallelic variants in CRIPT cause a Rothmund-Thomson-like syndrome with increased cellular senescence
Luisa Averdunk1, Maxim A Huetzen2, Daniel Moreno-Andrés3
1Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany.
Summary
Rothmund-Thomson syndrome (RTS) is a rare genetic disorder. Biallelic variants in CRIPT gene cause an RTS-like syndrome with neurodevelopmental delay and epilepsy, sharing cellular senescence mechanisms with RECQL4 variants.
Area of Science:
- Genetics
- Cellular Biology
- Dermatology
Background:
- Rothmund-Thomson syndrome (RTS) presents with poikiloderma, sparse hair, short stature, skeletal defects, cancer, and cataracts, mimicking premature aging.
- RECQL4 and ANAPC1 are the primary known genes implicated in over 70% of RTS cases.
- This study investigates novel genetic factors contributing to RTS-like phenotypes.
Purpose of the Study:
- To identify and characterize individuals with Rothmund-Thomson syndrome-like features associated with biallelic variants in the CRIPT gene.
- To compare the clinical and cellular characteristics of individuals with CRIPT variants to those with established RTS.
- To elucidate the molecular mechanisms underlying CRIPT-associated disorders.
Main Methods:
- Systematic comparison of clinical data from individuals with CRIPT variants and RTS patients.
- Computational analysis of facial photographs for phenotypic similarity.
- Histologic examination of skin biopsies and cellular studies on patient-derived fibroblasts.
Main Results:
- Individuals with CRIPT variants met RTS diagnostic criteria and exhibited neurodevelopmental delay and seizures.
- Computational analysis confirmed significant facial similarity between CRIPT and RTS individuals.
- CRIPT-deficient fibroblasts showed elevated senescence markers and increased senescence-associated ß-galactosidase activity, similar to RECQL4-deficient cells.
Conclusions:
- CRIPT variants cause an RTS-like syndrome that includes neurodevelopmental delay and epilepsy.
- CRIPT deficiency leads to cellular senescence, suggesting shared molecular pathways with RECQL4 in RTS pathogenesis.
- CRIPT represents a newly identified gene associated with Rothmund-Thomson syndrome spectrum disorders.
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