RGD Reference Report - Mutations in the mitochondrial seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA syndrome. - Rat Genome Database

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Mutations in the mitochondrial seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA syndrome.

Authors: Belostotsky, Ruth  Ben-Shalom, Efrat  Rinat, Choni  Becker-Cohen, Rachel  Feinstein, Sofia  Zeligson, Sharon  Segel, Reeval  Elpeleg, Orly  Nassar, Suheir  Frishberg, Yaacov 
Citation: Belostotsky R, etal., Am J Hum Genet. 2011 Feb 11;88(2):193-200. doi: 10.1016/j.ajhg.2010.12.010. Epub 2011 Jan 20.
RGD ID: 41410777
Pubmed: (View Article at PubMed) PMID:21255763
DOI: Full-text: DOI:10.1016/j.ajhg.2010.12.010

An uncharacterized multisystemic mitochondrial cytopathy was diagnosed in two infants from consanguineous Palestinian kindred living in a single village. The most significant clinical findings were tubulopathy (hyperuricemia, metabolic alkalosis), pulmonary hypertension, and progressive renal failure in infancy (HUPRA syndrome). Analysis of the consanguineous pedigree suggested that the causative mutation is in the nuclear DNA. By using genome-wide SNP homozygosity analysis, we identified a homozygous identity-by-descent region on chromosome 19 and detected the pathogenic mutation c.1169A>G (p.Asp390Gly) in SARS2, encoding the mitochondrial seryl-tRNA synthetase. The same homozygous mutation was later identified in a third infant with HUPRA syndrome. The carrier rate of this mutation among inhabitants of this Palestinian isolate was found to be 1:15. The mature enzyme catalyzes the ligation of serine to two mitochondrial tRNA isoacceptors: tRNA(Ser)(AGY) and tRNA(Ser)(UCN). Analysis of amino acylation of the two target tRNAs, extracted from immortalized peripheral lymphocytes derived from two patients, revealed that the p.Asp390Gly mutation significantly impacts on the acylation of tRNA(Ser)(AGY) but probably not that of tRNA(Ser)(UCN). Marked decrease in the expression of the nonacylated transcript and the complete absence of the acylated tRNA(Ser)(AGY) suggest that this mutation leads to significant loss of function and that the uncharged transcripts undergo degradation.



Disease Annotations    
HUPRA Syndrome  (IAGP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Sars2  (seryl-tRNA synthetase 2, mitochondrial)

Genes (Mus musculus)
Sars2  (seryl-aminoacyl-tRNA synthetase 2)

Genes (Homo sapiens)
SARS2  (seryl-tRNA synthetase 2, mitochondrial)


Additional Information