Leopard-like retinopathy and severe early-onset portal hypertension expand the phenotype of KARS1-related syndrome: a case report
Tóm tắt
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. 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. 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.
Tài liệu tham khảo
Fujishima K, Kanai A. tRNA gene diversity in the three domains of life. Front Genet. 2014;5:142.
Tolkunova E, Park H, Xia J, King MP, Davidson E. The human lysyl-tRNA synthetase gene encodes both the cytoplasmic and mitochondrial enzymes by means of an unusual alternative splicing of the primary transcript. J Biol Chem. 2000;275:35063–9.
McLaughlin HM, Sakaguchi R, Liu C, Igarashi T, Pehlivan D, Chu K, et al. Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy. Am J Hum Genet. 2010;87:560–6.
Santos-Cortez RLP, Lee K, Azeem Z, Antonellis PJ, Pollock LM, Khan S, et al. Mutations in KARS, encoding lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89. Am J Hum Genet. 2013;93:132–40.
Walker UA, Collins S, Byrne E. Respiratory chain encephalomyopathies: a diagnostic classification. Eur Neurol. 1996;36:260–7.
Ardissone A, Tonduti D, Legati A, Lamantea E, Barone R, Dorboz I, et al. KARS-related diseases: progressive leukoencephalopathy with brainstem and spinal cord calcifications as new phenotype and a review of literature. Orphanet J Rare Dis. 2018;13:45.
Itoh M, Dai H, Horike S-I, Gonzalez J, Kitami Y, Meguro-Horike M, et al. Biallelic KARS pathogenic variants cause an early-onset progressive leukodystrophy. Brain J Neurol. 2019;142:560–73.
Schouten JN, Verheij J, Seijo S. Idiopathic non-cirrhotic portal hypertension: a review. Orphanet J Rare Dis. 2015;10:67.
Clayman HM, Flynn JT, Koch K, Israel C. Retinal pigment epithelial abnormalities in leukemic disease. Am J Ophthalmol. 1972;74:416–9.
Schepens CL, Brockhurst RJ. Uveal effusion. 1. Clinical picture. Arch Ophthalmol Chic Ill. 1963;70:189–201.
Cohen SY, Quentel G, Egasse D, Cadot M, Ingster-Moati I, Coscas GJ. The dark choroid in systemic argyrosis. Retina Phila Pa. 1993;13:312–6.
Zürcher M. Schipper I [Spot-like to reticular pigment displacement in a patient with pseudoxanthoma elasticum (Grönblad-Strandberg syndrome)]. Klin Monatsbl Augenheilkd. 1990;196:30–2.
Barth RA, Pagon RA, Bunt-Milam AH. “Leopard spot” retinopathy in Warburg syndrome. Ophthalmic Paediatr Genet. 1986;7:91–6.
Sorcinelli R, Sitzia A, Figus A, Lai ME. Ocular findings in beta-thalassemia. Metab Pediatr Syst Ophthalmol N Y N. 1985;1990(13):23–5.
Lyons CJ, Castano G, McCormick AQ, Applegarth D. Leopard spot retinal pigmentation in infancy indicating a peroxisomal disorder. Br J Ophthalmol. 2004;88:191–2.
Jabbarpoor Bonyadi MH, Ownagh V, Rahimy E, Soheilian M. Giraffe or leopard spot chorioretinopathy as an outstanding finding: case report and literature review. Int Ophthalmol. 2019;39:1405–12.