title: Pyrimidine-5'-nucleotidase Campinas, a new mutation (p.R56G) in the NT5C3 gene associated with pyrimidine-5'-nucleotidase type I deficiency and influence of Gilbert's Syndrome on clinical expression.
abstract: Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans.
authors.affiliation: Hemocentro e Instituto Nacional de Ciência e Tecnologia do Sangue, Universidade de Campinas, São Paulo, Brazil.
authors.forename: Andrey dos
authors.initials: Ad
authors.lastname: Santos
authors.affiliation: Hemocentro e Instituto Nacional de Ciência e Tecnologia do Sangue, Universidade de Campinas, São Paulo, Brazil.
authors.forename: Larissa Elizabeth Cordeiro
authors.initials: LE
authors.lastname: Dantas
authors.affiliation: Hemocentro e Instituto Nacional de Ciência e Tecnologia do Sangue, Universidade de Campinas, São Paulo, Brazil.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Traina
authors.affiliation: Hemocentro e Instituto Nacional de Ciência e Tecnologia do Sangue, Universidade de Campinas, São Paulo, Brazil.
authors.forename: Dulcineia Martins de
authors.initials: DM
authors.lastname: Albuquerque
authors.affiliation: Hemocentro e Instituto Nacional de Ciência e Tecnologia do Sangue, Universidade de Campinas, São Paulo, Brazil.
authors.forename: Elinton Adami
authors.initials: EA
authors.lastname: Chaim
authors.affiliation: Hemocentro e Instituto Nacional de Ciência e Tecnologia do Sangue, Universidade de Campinas, São Paulo, Brazil. Electronic address: sara@unicamp.br.
authors.forename: Sara T Olalla
authors.initials: ST
authors.lastname: Saad
mesh_terms: D015720:5'-Nucleotidase / Q000172:deficiency* / Q000235:genetics; D000328:Adult; D000483:Alleles; D000745:Anemia, Hemolytic, Congenital / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002648:Child; D002779:Cholestasis / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D003241:Consanguinity; D004843:Epistasis, Genetic; D005260:Female; D005878:Gilbert Disease / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006023:Glycoproteins / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D019190:Iron Overload / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D006023:Glycoproteins; D015720:5'-Nucleotidase; C412794:NT5C3A protein, human
keywords: Gilbert's Syndrome; Iron overload; Liver disease; P5′N; Pyrimidine-5′-nucleotidase