Abstract
Methionyl-tRNA synthetase (MARS) catalyzes the ligation of methionine to tRNA. Heterozygous MARS mutations have been reported to cause Charcot-Marie-Tooth disease, axonal, type 2U (CMT2U). Homozygous or compound heterozygous mutations in MARS gene would cause interstitial lung and liver disease (ILLD), a severe disease onset in infancy or early childhood. Here we report a Chinese ILLD family with two affected boys diagnosed by exome sequencing. They carry novel compound heterozygous MARS mutations (p.Asp145Asn and p.Phe802Ser). Their phenotype is concordant with ILLD description. As ILLD patients were only reported by two studies, we summarized all the reported patients and characterized the principle clinical features as interstitial lung disease, developmental delay, postnatal growth failure, non-life-threatening liver dysfunction and anemia. Genotype–phenotype correlation analysis suggests most of the ILLD mutations locate in the catalytic domain of MARS. ILLD and CMT2U might have different disease mechanism.
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Acknowledgements
We thank the patients and their family members for their participation. This work was funded by National Natural Science Foundation of China (81400872 to YS, 81170811, 30973216 to WJQ), and Shanghai Health Bureau (20134005 to WJQ).
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Sun, Y., Hu, G., Luo, J. et al. Mutations in methionyl-tRNA synthetase gene in a Chinese family with interstitial lung and liver disease, postnatal growth failure and anemia. J Hum Genet 62, 647–651 (2017). https://doi.org/10.1038/jhg.2017.10
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DOI: https://doi.org/10.1038/jhg.2017.10
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