Molecular analysis of the AGXT gene in patients suspected with hyperoxaluria type 1 and three novel mutations from Turkey

作者：Isiyel Emel^*; Ezgu Sevcan A Bakkaloglu; Caliskan Salim; Akman Sema; Akil Ipek; Tabel Yilmaz; Akinci Nurver; Ozdogan Elif Bahat; Ozel Ahmet; Eroglu Fehime Kara; Ezgu Fatih S

来源：Molecular Genetics and Metabolism, 2016, 119(4): 311-316.

DOI：10.1016/j.ymgme.2016.10.011

• Primary hyperoxaluria type 1
• Alanine glyoxylateaminotransferase (AGXT) gene mutation

Primary hyperoxaluria type 1 (PH1) is a rare, autosomal recessive disease, caused by the defect of AGXT gene encoding hepatic peroxisomal alanine glyoxylateaminotransferase (AGT). This enzyme is responsible for the conversion of glyoxylate to glycine. The diagnosis of PH1 should be suspected in infants and children with nephrocalcinosis or nephrolithiasis. Early diagnosis and treatment is crucial in preventing disease progression to end stage kidney disease (ESKD).
In this study, AGXT gene sequence analyses were performed in 82 patients who were clinically suspected (hyperoxaluria and nephrolithiasis or nephrocalcinosis with or without renal impairment) to have PH1. Disease causing mutations have been found in fifteen patients from thirteen families (18%). Novel mutations have been found (c.458T > A (p.L153X), c.733_734delAA (p.Lys245Valfs*11), c.52 C > T (p.L18F)) in three of 13 families. There were 3-year lag time between initial symptoms and the time of PH1 is suspected; additionally, 5.5-year lag time between initial symptoms and definitive diagnosis. Consanguinity was detected in 77% of the patients with mutation. After genetic diagnosis, one patient received combined kidney and liver transplantation.
AGXT gene sequencing is now the choice of diagnosis of PH1 due to its non-invasive nature compared to liver enzyme assay. Early diagnosis and accurate treatment in PH1 is important for better patient outcomes.

• 出版日期2016-12