Novel homozygous RARS2 mutation in two siblings without pontocerebellar hypoplasia - Further expansion of the phenotypic spectrum

Orphanet Journal of Rare Diseases

Volumn 11, Issue 1, 2016, Pages

  Luhl S ^a   Bode, H ^a   Schlotzer W ^a   Bartsakoulia, M ^b   Horvath, R ^b   Abicht, A ^c   Stenzel, M ^d   Kirschner, J ^e   Grunert S C ^e  

^a UNIVERSITY HOSPITAL ULM   (Germany)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

^c Medical Genetic Centre   (Germany)

^d Kliniken der Stadt Koln   (Germany)

^e UNIVERSITY OF FREIBURG   (Germany)

Author keywords

Mitochondrial arginyl transfer RNA synthetase; Mitochondrial disease; OXPHOS; Pontocerebellar hypoplasia; RARS2

Indexed keywords

ARTICLE; ASYMPTOMATIC DISEASE; CASE REPORT; CHILD; CLINICAL FEATURE; COMPARATIVE GENOMIC HYBRIDIZATION; DEVELOPMENTAL DISORDER; DISEASE SEVERITY; EXON; FEMALE; FIBROBLAST; GENETIC CODE; HOMOZYGOSITY; HUMAN; HUMAN CELL; LACTIC ACIDOSIS; MALE; MICROCEPHALY; MUTATIONAL ANALYSIS; MUTATOR GENE; NUCLEAR MAGNETIC RESONANCE IMAGING; OXYGEN CONSUMPTION; PHENOTYPE; POLYACRYLAMIDE GEL ELECTROPHORESIS; RARS2 GENE; SEIZURE; SIBLING; DISORDERS OF MITOCHONDRIAL FUNCTIONS; GENETICS; INFANT; MUTATION; NEWBORN; OLIVOPONTOCEREBELLAR ATROPHY; PATHOLOGY; PRESCHOOL CHILD;

ARGININE TRANSFER RNA LIGASE; RARS2 PROTEIN, HUMAN;

ARGININE-TRNA LIGASE; CHILD, PRESCHOOL; FEMALE; HUMANS; INFANT; INFANT, NEWBORN; MAGNETIC RESONANCE IMAGING; MALE; MITOCHONDRIAL DISEASES; MUTATION; OLIVOPONTOCEREBELLAR ATROPHIES; SIBLINGS;

EID: 84992128560     PISSN: None     EISSN: 17501172     Source Type: Journal    
DOI: 10.1186/s13023-016-0525-9     Document Type: Article

References (16)

1. Lax NZ, Alston CL, Schon K, Park SM, Krishnakumar D, He L, Falkous G, Ogilvy-Stuart A, Lees C, King RH, et al. Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations. J Neuropathol Exp Neurol. 2015;74(7):688-703.
2. Edvardson S, Shaag A, Kolesnikova O, Gomori JM, Tarassov I, Einbinder T, Saada A, Elpeleg O. Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. Am J Hum Genet. 2007;81(4):857-62.
3. Cassandrini D, Cilio MR, Bianchi M, Doimo M, Balestri M, Tessa A, Rizza T, Sartori G, Meschini MC, Nesti C, et al. Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: definition of the clinical spectrum and molecular findings in five patients. J Inherit Metab Dis. 2013;36(1):43-53.
4. den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, Roux AF, Smith T, Antonarakis SE, Taschner PE. HGVS Recommendations for the Description of Sequence Variants: 2016 Update. Hum Mutat. 2016;37(6):564-9.
5. Invernizzi F, D'Amato I, Jensen PB, Ravaglia S, Zeviani M, Tiranti V. Microscale oxygraphy reveals OXPHOS impairment in MRC mutant cells. Mitochondrion. 2012;12(2):328-35.
6. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54.
7. Ng PC, Henikoff S. SIFT: Predicting amino acid changes that affect protein function. Nucleic Acids Res. 2003;31(13):3812-4.
8. Ramensky V, Bork P, Sunyaev S. Human non-synonymous SNPs: server and survey. Nucleic Acids Res. 2002;30(17):3894-900.
9. Rankin J, Brown R, Dobyns WB, Harington J, Patel J, Quinn M, Brown G. Pontocerebellar hypoplasia type 6: A British case with PEHO-like features. Am J Med Genet A. 2010;152A(8):2079-84.
10. Li Z, Schonberg R, Guidugli L, Johnson AK, Arnovitz S, Yang S, Scafidi J, Summar ML, Vezina G, Das S, et al. A novel mutation in the promoter of RARS2 causes pontocerebellar hypoplasia in two siblings. J Hum Genet. 2015;60(7):363-9.
11. Glamuzina E, Brown R, Hogarth K, Saunders D, Russell-Eggitt I, Pitt M, de Sousa C, Rahman S, Brown G, Grunewald S. Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2. J Inherit Metab Dis. 2012;35(3):459-67.
12. Joseph JT, Innes AM, Smith AC, Vanstone MR, Schwartzentruber JA, Bulman DE, Majewski J, Daza RA, Hevner RF, Michaud J, et al. Neuropathologic features of pontocerebellar hypoplasia type 6. J Neuropathol Exp Neurol. 2014;73(11):1009-25.
13. Ngoh A, Bras J, Guerreiro R, Meyer E, McTague A, Dawson E, Mankad K, Gunny R, Clayton P, Mills PB, et al. RARS2 mutations in a sibship with infantile spasms. Epilepsia. 2016;57(5):e97-e102.
14. Nishri D, Goldberg-Stern H, Noyman I, Blumkin L, Kivity S, Saitsu H, Nakashima M, Matsumoto N, Leshinsky-Silver E, Lerman-Sagie T, et al. RARS2 mutations cause early onset epileptic encephalopathy without ponto-cerebellar hypoplasia. Eur J Paediatr Neurol. 2016;20(3):412-7.
15. Kastrissianakis K, Anand G, Quaghebeur G, Price S, Prabhakar P, Marinova J, Brown G, McShane T. Subdural effusions and lack of early pontocerebellar hypoplasia in siblings with RARS2 mutations. Arch Dis Child. 2013;98(12):1004-7.
16. Alkhateeb AM, Aburahma SK, Habbab W, Thompson IR. Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability. Metab Brain Dis. 2016;31(4):901-7.