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Updated: Jan 18, 2026
09:34
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
34.6K
LONP1 Variants Are Associated With Clinically Diverse Phenotypes.
Randee E Young1, Lu Qiao2,3, Rebecca Hernan1
1Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Clinical Genetics
|September 10, 2025
Summary
Genetic variants in LONP1, a mitochondrial protease, cause a range of developmental disorders. This study identifies 16 new variants, expanding the known clinical spectrum of LONP1-associated conditions.
Area of Science:
- Genetics
- Molecular Biology
- Developmental Biology
Background:
- LONP1 is a mitochondrial protease crucial for protein homeostasis and cellular metabolism.
- Genetic variants in LONP1 are linked to diverse disorders including CODAS syndrome, congenital diaphragmatic hernia (CDH), and neurodevelopmental disorders (NDD).
Purpose of the Study:
- To identify novel variants in the LONP1 gene.
- To expand the understanding of the clinical and genetic spectrum of LONP1-associated disorders.
- To investigate the structural and mechanistic basis of genotype-phenotype correlations.
Main Methods:
- Whole-exome sequencing or targeted gene sequencing.
- Clinical data review of affected individuals.
- Structural analysis of identified variants within the LONP1 protein.
Main Results:
- Sixteen novel LONP1 variants were identified in 16 individuals, including 11 with NDD and 5 with CDH.
- Structural mapping indicated phenotype-specific clustering of missense variants.
- CODAS is associated with biallelic loss-of-function variants, while CDH is linked to monoallelic loss-of-function variants.
Conclusions:
- The study expands the phenotypic and genetic landscape of LONP1-related disorders.
- LONP1 plays a critical role in human development and mitochondrial function.
- Both monoallelic and biallelic LONP1 variants contribute to NDD, suggesting complex pathogenic mechanisms.
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