Primary hyperoxaluria (PH) is a rare autosomal recessive disease, com¬monly arising in childhood with nephrolithiasis, nephrocalcinosis, chronic renal failure. Mutations in AGXT, GRHPR and HOGA1 genes are responsible of type 1, 2 and 3 respectively. Our laboratory, member of the European PH consortium (OxalEurope), is the only Italian center offering these genetic analyses. Currently, 81 AGXT-PH1 and 1 GRHPR-PH2 patient are known in Italy. In this study the entire coding sequence of GRHPR and HOGA1 genes and the AGXT promoter was sequenced in 15 patients with high clinical suspicion of PH, negative for AGXT mutations. No point mutations were detected. One patient resulted homozygous for the c.341-81delT HOGA1 variant in intron 2. This variant is not reported in literature and was evaluated as pa¬thogenic by in silico prediction, generating a new acceptor splicing site (AG in c.341-79). The minigene in-vitro assay demonstrated that this variant did not interfere with splicing. Two patients were heterozygous for two different AGXT-promoter variants (c.-647C>T, c.-424C>T), not reported in the scarce literature nor in 1000Ge¬nomes Database. These variants have been evaluated as not pathogenic be¬cause they do not lie in any known regulatory-transcription site. The negative results in those patients with high clinical suspicion of PH could be explained by undetected deletions (investigable by MLPA analysis of the two major genes) or mutations in other genes involved in oxalate me¬tabolism, or differential diagnosis.
Primary hyperoxaluria: analysis of GRHPR, HOGA1 genes and the promoter-sequence of AGXT gene in the Italian population / A. Pelle; G. Mandrile; A. Cuccurullo; C. Mancini; R. Sebastiano; S. Varacalli; D. F. Giachino; M. De Marchi. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - ELETTRONICO. - Volume 22 May 2014:Supplement 1(2014), pp. 93-94. ((Intervento presentato al convegno European Human Genetics Conference 2014 tenutosi a Milan, Italy nel May 31 - June 3, 2014.