A Novel Homozygous Missense Mutation in the YARS Gene: Expanding the Phenotype of YARS Multisystem Disease
| Autor: | Shanelle J De Lancy, Lori-Anne Schillaci, Tricia R. Bhatti, Rawah K H M Zeiad, Demitrios Dedousis, Amanda M. Ackermann, Maricruz Crespo, Jamie R Wood, Edwin C Ferren, Jirair K. Bedoyan, Shahrazad T. Saab, Denise D Young, Raymond W. Redline |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
tyrosyl-tRNA synthetase medicine.medical_specialty Endocrinology Diabetes and Metabolism Case Reports 030105 genetics & heredity Hypoglycemia medicine.disease_cause Gastroenterology 03 medical and health sciences Internal medicine medicine Missense mutation Global developmental delay Exocrine pancreatic insufficiency Hyperinsulinemic hypoglycemia Exome sequencing multisystem disease business.industry Chronic liver disease YARS medicine.disease Hypotonia 030104 developmental biology Congenital hyperinsulinism hyperinsulinemic hypoglycemia medicine.symptom business AcademicSubjects/MED00250 |
| Zdroj: | Journal of the Endocrine Society |
| ISSN: | 2472-1972 |
| Popis: | Aminoacyl-tRNA synthetases (ARSs) are crucial enzymes for protein translation. Mutations in genes encoding ARSs are associated with human disease. Tyrosyl-tRNA synthetase is encoded by YARS which is ubiquitously expressed and implicated in an autosomal dominant form of Charcot-Marie-Tooth and autosomal recessive YARS-related multisystem disease. We report on a former 34-week gestational age male who presented at 2 months of age with failure to thrive (FTT) and cholestatic hepatitis. He was subsequently diagnosed with hyperinsulinemic hypoglycemia with a negative congenital hyperinsulinism gene panel and F-DOPA positron-emission tomography (PET) scan that did not demonstrate a focal lesion. Autopsy findings were notable for overall normal pancreatic islet size and morphology. Trio whole exome sequencing identified a novel homozygous variant of uncertain significance in YARS (c.611A > C, p.Tyr204Cys) with each parent a carrier for the YARS variant. Euglycemia was maintained with diazoxide (max dose, 18 mg/kg/day), and enteral dextrose via gastrostomy tube (G-Tube). During his prolonged hospitalization, the patient developed progressive liver disease, exocrine pancreatic insufficiency, acute renal failure, recurrent infections, ichthyosis, hematologic concerns, hypotonia, and global developmental delay. Such multisystem features have been previously reported in association with pathogenic YARS mutations. Although hypoglycemia has been associated with pathogenic YARS mutations, this report provides more conclusive data that a YARS variant can cause hyperinsulinemic hypoglycemia. This case expands the allelic and clinical heterogeneity of YARS-related disease. In addition, YARS-related disease should be considered in the differential of hyperinsulinemic hypoglycemia associated with multisystem disease. |
| Databáze: | OpenAIRE |
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