Next-generation sequencing in identification of pathogenic variants in primary hyperoxaluria among 21 Egyptian families: Identification of two novel AGXT gene mutations.
- Citation:
- Next-generation sequencing in identification of pathogenic variants in primary hyperoxaluria among 21 Egyptian families: Identification of two novel AGXT gene mutations., Ahmed, Hoda A., Fadel Fatina I., Abdel Mawla Mohamed A., Salah Doaa M., Fathallah Mohamed Gamal, and Amr Khalda , Molecular genetics & genomic medicine, (2022)
Abstract:
BACKGROUND: Primary hyperoxaluria (PH) is a rare heterogeneous, autosomal recessive disorder of glyoxylate metabolism. It is characterized by excessive hepatic production of oxalate resulting in a wide spectrum of clinical, imaging, and functional presentation. The characteristic features of PH comprise of recurrent urolithiasis, renal stones, and/or nephrocalcinosis. Three known types of PH have been identified PH1, PH2, and PH3. Pathogenic variants in AGXT, GRHPR, and HOGA1 cause the phenotypic expression of PH.
METHODS: In this study, we describe the clinical and genetic findings of 22 patients from 21 unrelated Egyptian families with the distinctive clinical features of PH. A thorough clinical evaluation followed by an NGS custom panel of AGXT, GRHPR, and HOGA1 genes was done.
RESULTS: Two novel mutations (p.Gly27Glu and p.Gln256Serfs*17) and six previously reported mutations (p.Lys12Glnfs*156, p.Lys12Argfs*34, p.Ile244Thr, p.Asn22Ser, p.Pro11Leu, and p.Ile340Met) were identified in AGXT gene. The NGS panel results were validated thereafter using Sanger sequencing.
CONCLUSION: Our results extend the number of AGXT mutations identified so far and emphasize the important role of genetic testing in providing proper counseling and patients management.