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Loss-of-Function CARS1 Variants in a Patient With Microcephaly, Developmental Delay, and a Brittle Hair Phenotype
Christina Del Greco1, Molly E Kuo1,2,3, Desiree E C Smith4
1Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, USA.
Mutations in cysteinyl-tRNA synthetase (CARS1) cause a rare multisystem disease. This study details a patient with novel CARS1 variants, expanding the known genetic causes and symptoms of this condition.
Area of Science:
- Genetics
- Molecular Biology
- Rare Diseases
Background:
- Mutations in cysteinyl-tRNA synthetase (CARS1) are linked to multisystem disorders.
- Associated phenotypes include microcephaly, developmental delay, and brittle hair/nails.
Purpose of the Study:
- To investigate the genetic basis of a patient presenting with a complex set of symptoms.
- To characterize the functional impact of identified CARS1 variants.
Main Methods:
- Whole exome sequencing was performed to identify genetic variants.
- Yeast complementation assays were used to assess the functional consequences of identified variants.
Main Results:
- The patient was found to be compound heterozygous for two CARS1 variants: p.Arg341His and p.Arg370Trp.
- Functional assays revealed p.Arg341His as a hypomorphic variant and p.Arg370Trp as a loss-of-function variant.
Conclusions:
- This report expands the known allelic and phenotypic spectrum of CARS1-associated disease.
- It highlights the importance of CARS1 in human health and disease.
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