| Popis: |
Abstract Background Hyperuricemia, pulmonary hypertension, renal failure, and alkaline intoxication syndrome (HUPRA syndrome) is a rare autosomal recessive mitochondrial disease. SARS2 gene encoding seryl‐tRNA synthetase is the only pathogenic gene of HUPRA syndrome. All the previously reported cases with HUPRA syndrome were detected for homozygous mutation. Methods We identified compound heterozygous mutations causing HUPRA syndrome using whole‐exome sequencing, and verifed pathogenicity with ACMG standards. All the previously published cases with SARS2 mutations were reviewed. Results SARS2 gene compound heterozygotes variants were detected in this Chinese patient (c.667G>A/c.1205G>A). Bioinformatics studies and protein models predict that a new variant (c.667G>A) is likely to be pathogenic. A total of six patients, five of whom were previously reported with HUPRA syndrome, were analyzed. All of the six had typical clinical manifestations of HUPRA syndrome, except the Chinese girl who had no pulmonary hypertension or alkaline intoxication. The shrunken kidney was more prominent in our proband. The average survival time for previously reported patients was 17 months, and the Chinese girl was 70 months. Three mutation variants were found, including five homozygous mutants, three of which were Palestinian (c.1169A > G), two of which were from a Spanish family (c.1205G> A), and one was a new variant (c.667G>A/c.1205G>A). Conclusion We found a new pathogenic form (compound heterozygous mutation) causing HUPRA syndrome, and identified a novel pathogenic site (c.667G>A) of the SARS2 gene, expanding the spectrum of SARS2 pathogenic variants. The mild phenotype in complex heterozygous mutations is described. |
