Mutation spectrum and genotype-phenotype correlation in a cohort of Argentine patients with ornithine transcarbamylase deficiency: a single center experience

• Autores: Laróvere, Laura Elena; Silvera Ruiz, Silene M.; Arranz, José A.; Dodelson de Kremer, Raquel
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: UREA CYCLE DISORDERS; ORNITHINE TRANSCARBAMYLASE DEFICIENCY; OTC MUTATIONS; HYPERAMMONEMIA
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

X-linked ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder. Hemizygous males with complete deficiency manifest neonatal acute hyperammonemia, while those with partial deficiency have a late presentation. The symptomatology of heterozygotes depends on the inactivation pattern of X chromosome. Hyperammonemic episodes can cause neurological damage and are potentially fatal. Here, we match clinical, biochemical, and molecular findings with bioinformatics analyses to report genotype–phenotype correlations in 14 Argentine patients with OTCD from 11 unrelated families: 4 hemizygotes with neonatal onset (complete OTC gene deletion, 533C > T, c.540+1G > A, c.697delG); 4 hemizygotes with late onset (c.216+1G > A, c.386G > A, c.622G > A, c.829C > T); and 6 symptomatic heterozygotes (complete OTC gene deletion, c.533C > T, c.452T > G, c.540+1G > A, dupE1-9/delE10). Three of these mutations were previously unreported: c.540+1G > A, c.697delG, and dup1-9/del10. Our data highlight the relevance of combining molecular and bioinformatics analyses for accurate diagnosis and outcome prediction in suspected patients with OTCD and the importance of carrier testing for effective genetic counseling.
Fil: Laróvere, Laura Elena. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Silvera Ruiz, Silene M.. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina
Fil: Arranz, José A.. Hospital Vall Dhebron; España
Fil: Dodelson de Kremer, Raquel. Universidad Nacional de Cordoba. Facultad de Medicina. Centro de Estudios de las Metabolopatías Congénitas; Argentina