Bi‐allelic KARS1 pathogenic variants affecting functions of cytosolic and mitochondrial isoforms are associated with a progressive and multisystem disease

Abstract

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KARS‐related diseases with macrothrombocytes and pulmonary arterial hypertension

“…In the hematological system, KARS ‐related diseases have been associated with anemia, neutropenia, thrombocytopenia, and pancytopenia without any morphological description (domestic cases in Table S2). 1,2 In our patients, erythroid and myeloid systems were not affected. As shown in the platelet vacuolization, mitochondrial dysfunction might relate to unstable blood cells.…”

“…KARS abnormality often causes mitochondrial dysfunction, showing a lactate peak in magnetic resonance spectroscopy (MRS) and mitochondrial respiratory chain abnormalities in fibroblasts 1 . Patient 2 had abnormalities in MRS and fibroblast consumption rate, which means that there was mitochondrial dysfunction and abnormal oxidative metabolism 3 .…”

The best of both worlds: Blending cutting‐edge research with clinical processes for a productive exome clinic

“…Data from this study have been included in 32 publications, including novel gene‐disease associations, 38–46 novel phenotypes 24–28 and phenotype expansions 29–37 for ultra‐rare disorders.…”

“…Most of the 138 definite/likely diagnoses were known disorders (n = 115, 83%); the remaining were new phenotypes for genes previously known to be associated with disease (n = 5, 3.6%) [24][25][26][27][28] and phenotypic expansions for known disorders (n = 9, 6.5%). [29][30][31][32][33][34][35][36][37] Additionally, nine new gene-disease associations (6.5% of the def/likely diagnoses) were established.…”

“…Data from this study have been included in 32 publications, including novel gene-disease associations, [38][39][40][41][42][43][44][45][46] novel phenotypes [24][25][26][27][28] and phenotype expansions [29][30][31][32][33][34][35][36][37] for ultra-rare disorders. For the fourth patient, the UDN prioritized a homozygous missense variant in a gene that had in the interim been associated with a disease.…”