RESUMO
BACKGROUND: Selective intestinal cobalamin malabsorption with mild proteinuria (Imerslund-Gräsbeck syndrome; I-GS), is an autosomal recessive disorder of dogs caused by mutations in AMN or CUBN that disrupt cubam function and which can present as a medical emergency. OBJECTIVES: To describe the clinical, metabolic, and genetic bases of I-GS in Beagles. ANIMALS: Four cobalamin-deficient and 43 clinically normal Beagles and 5 dogs of other breeds. METHODS: Clinical description and candidate gene genetic study. Urinary organic acid and protein excretion were determined by gas-chromatography and SDS-PAGE, respectively. Renal cubilin protein expression was assessed on immunoblots. Mutation discovery was carried out by PCR amplification and DNA sequencing of exons with flanking splice sites and cDNA of CUBN and AMN. Genotyping was performed by restriction enzyme digestion of PCR amplicons. RESULTS: Juvenile-affected Beagles exhibited failure to thrive, dyshematopoiesis with neutropenia, serum cobalamin deficiency, methylmalonic aciduria, hyperammonemia, and proteinuria. Affected dogs' kidneys lacked detectable cubilin protein. All affected dogs were homozygous for a single-base deletion in CUBN exon 8 (CUBN c.786delC), predicting a translational frameshift, and the 2 parents tested were heterozygous. CONCLUSIONS: The CUBN mutation in juvenile I-GS Beagles causes a more severe cobalamin malabsorption than in Border Collies with a different CUBN defect, but is similar to I-GS caused by AMN mutations in Giant Schnauzers and Australian Shepherds. Awareness of the disorder and breed predispositions to I-GS is crucial to precisely diagnose and promptly treat hereditary cobalamin malabsorption and to prevent disease in those dogs at risk in future generations.
Assuntos
Doenças do Cão/patologia , Síndromes de Malabsorção/veterinária , Proteinúria/veterinária , Deficiência de Vitamina B 12/veterinária , Anemia Megaloblástica , Animais , Sequência de Bases , Doenças do Cão/genética , Doenças do Cão/metabolismo , Cães , Éxons/genética , Feminino , Mutação da Fase de Leitura/genética , Predisposição Genética para Doença/genética , Genótipo , Síndromes de Malabsorção/genética , Síndromes de Malabsorção/metabolismo , Síndromes de Malabsorção/patologia , Masculino , Glicoproteínas de Membrana/genética , Dados de Sequência Molecular , Proteinúria/genética , Proteinúria/metabolismo , Proteinúria/patologia , Deficiência de Vitamina B 12/genética , Deficiência de Vitamina B 12/metabolismo , Deficiência de Vitamina B 12/patologiaRESUMO
After more than 20 years the extended pedigree of the only known kindred carrying the low frequency antigen Ria (Ridley) was reinvestigated. It is established that Ria is governed by a gene which is part of or very closely linked to the MNSs locus. Further serological and frequency studies are reported.
Assuntos
Sistema do Grupo Sanguíneo MNSs , Quimotripsina/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Feminino , Sangue Fetal/análise , Ligação Genética , Humanos , Isoanticorpos/análise , Isoantígenos/análise , Masculino , Papaína/farmacologia , Linhagem , Pronase/farmacologia , Tripsina/farmacologiaRESUMO
The second Pt(a+) family is described. Pta is shown to segregate independently from several genetic markers.
Assuntos
Antígenos de Grupos Sanguíneos , Genes , Sistema ABO de Grupos Sanguíneos , Sistema do Grupo Sanguíneo Duffy , Feminino , Antígenos HLA/genética , Humanos , Sistema do Grupo Sanguíneo MNSs , Masculino , Linhagem , Fenótipo , Recombinação Genética , Sistema do Grupo Sanguíneo Rh-HrRESUMO
A new low frequency antigen, Rba, has been found in three blood donors. Studies on their families show that the antigen is inherited as a Mendelian autosomal dominant character. Rba segregates independently from ABO, MNSs P1, Rh, Kell, Duffy, Kidd, ACP1 and PGM1. Anti-Rba is not common in sera containing multiple antibodies ot low frequency antigens.
