Francesca Peluso1, Viviana Palazzo2, Giuseppe Indolfi3, Francesco Mari4, Roberta Pasqualetti5, Elena Procopio6, Claudia Nesti1, Renzo Guerrini4, Filippo Santorelli1, Sabrina Giglio7,8. 1. Molecular Medicine, IRCCS Fondazione Stella Maris, Pisa, Italy. 2. Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy. 3. Paediatric and Liver Unit, Meyer Children's University Hospital, Florence, Italy. 4. Paediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Meyer Children's University Hospital, Florence, Italy. 5. Paediatric Ophthalmology Unit, Meyer Children's University Hospital, Florence, Italy. 6. Metabolic and Muscular Unit, Meyer Children's University Hospital of Florence, Florence, Italy. 7. Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy. sabrinar.giglio@unica.it. 8. Sabrina Giglio MD, PhD Unit of Medical Genetics, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy. sabrinar.giglio@unica.it.
Abstract
BACKGROUND: Mutations in lysyl-tRNA synthetase (KARS1), an enzyme that charges tRNA with the amino acid lysine in both the cytoplasm and mitochondria, have been associated thus far with autosomal recessive Charcot-Marie-Tooth type CMTRIB, hearing loss type DFNB89, and mitochondrial encephalohepatopathy (MEH) featuring neurodevelopmental disorders with microcephaly, white matter changes, and cardiac and hepatic failure in less than 30 patients. CASE PRESENTATION: We report the clinical, biochemical and molecular findings of a 14-month-old girl with severe MEH compatible clinical features, profound sensorineural hearing loss, leopard spot retinopathy, pancytopenia, and advanced liver disease with portal hypertension leading to death at the age of 30 months. CONCLUSIONS: Whole exome sequencing identified two rare variants in KARS1 gene. Our report expands the allelic and clinical features of tRNA synthase disorders. Moreover, with our report we confirm the usefulness of WES as first tier diagnostic method in infants with complex multisystem phenotypes.
BACKGROUND: Mutations in lysyl-tRNA synthetase (KARS1), an enzyme that charges tRNA with the amino acid lysine in both the cytoplasm and mitochondria, have been associated thus far with autosomal recessive Charcot-Marie-Tooth type CMTRIB, hearing loss type DFNB89, and mitochondrial encephalohepatopathy (MEH) featuring neurodevelopmental disorders with microcephaly, white matter changes, and cardiac and hepatic failure in less than 30 patients. CASE PRESENTATION: We report the clinical, biochemical and molecular findings of a 14-month-old girl with severe MEH compatible clinical features, profound sensorineural hearing loss, leopard spot retinopathy, pancytopenia, and advanced liver disease with portal hypertension leading to death at the age of 30 months. CONCLUSIONS: Whole exome sequencing identified two rare variants in KARS1 gene. Our report expands the allelic and clinical features of tRNA synthase disorders. Moreover, with our report we confirm the usefulness of WES as first tier diagnostic method in infants with complex multisystem phenotypes.
Entities:
Keywords:
ARSs; Case report; Encephalohepatopathy; KARS; Leopard-like retinopathy; Mitochondrial diseases
Authors: Regie Lyn P Santos-Cortez; Kwanghyuk Lee; Zahid Azeem; Patrick J Antonellis; Lana M Pollock; Saadullah Khan; Paula B Andrade-Elizondo; Ilene Chiu; Mark D Adams; Sulman Basit; Joshua D Smith; Deborah A Nickerson; Brian M McDermott; Wasim Ahmad; Suzanne M Leal Journal: Am J Hum Genet Date: 2013-06-13 Impact factor: 11.025