Journal
JOURNAL OF MOLECULAR DIAGNOSTICS
Volume 22, Issue 12, Pages 1373-1382Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jmoldx.2020.08.006
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Funding
- National Natural Science Foundation of China [31701138, 31701152]
- Shanghai Sailing Program [16YF1401000]
- China Postdoctoral Science Foundation [2020M681176]
- National Key Research and Development Program [2016YFC0905102, 2018YFC0116903]
- Science and Technology Commission of Shanghai Municipality [16ZR1446500]
- Shanghai Municipal Science and Technology Major Project [2017SHZDZX01]
- Shanghai Key Laboratory of Birth Defects [13DZ2260600]
- Shanghai Hospital Development Center [12017110]
- Research Projects of the Shanghai Municipal Health and Family Planning Committee [20174Y0026]
- Intelligent Medical Research Project of Shanghai Health and Family Planning Commission [2018ZHYL0225]
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The PYGL gene is the only established gene known to cause glycogen storage disease type VI (GSD6), which is a rare autosomal recessive disorder associated with hepatomegaly, elevated levels of hepatic transaminases, and hypoglycemia. Extended bioinformatics analysis was performed on the exome sequencing data of 5 patients who were clinically diagnosed as having or highly suspected of having GSD, and a single heterozygous pathogenic or likely pathogenic or rare variant of uncertain significance single-nucleotide variant was identified on the PYGL gene. A recurrent, novel, 3.6-kb deletion involving exons 14 to 17 of PYGL was identified in three of the five patients. Together with the two novel and one established stop-gain SNVs, they were diagnosed as compounds heterozygous of PYGL variants and confirmed as GSD6. The detected 3.6-kb deletion was further screened in a Chinese cohort of 31,317 individuals without hepatic abnormalities, and 10 carriers were identified, showing an allele frequency of 0.016%. Compared with the previously established 47 PYGL pathogenic or likely pathogenic SNVs, the novel pathogenic deletion had the second highest allele frequency among the population. This recurrent, novel, 3.6-kb deletion improved the molecular diagnostic rate of the GSD6. The relatively high frequency of the variant suggests that it is a potential mutation hotspot in patients with GSD6.
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