RESUMO
We report maternal uniparental disomy of chromosome 17 (mat UPD17) in a 2.5-year-old girl presenting infantile cystinosis. This patient was homozygous for the 57 kb deletion encompassing the CTNS gene, frequently found in patients from the European origin. The proband's mother was heterozygous for the deletion and the father did not carry the deletion. We carried out haplotype analysis with polymorphic markers spanning the whole chromosome 17. Informative markers showed the presence of two maternal alleles but no paternal allele for regions spanning the 17q arm and the proximal half of 17p, and only one maternal allele on the distal 17p arm. As deletion of half of 17p is probably not viable, these results suggest mat UPD17 with heterodisomy of 17q and proximal 17p and isodisomy of distal 17p. This is the first demonstration of mat UPD17, in particular of isodisomy 17p, in cystinosis.
Assuntos
Cromossomos Humanos Par 17 , Cistinose/genética , Nefropatias/genética , Dissomia Uniparental , Sistemas de Transporte de Aminoácidos Neutros/genética , Pré-Escolar , Cistinose/etiologia , Feminino , Humanos , Nefropatias/complicações , LinhagemAssuntos
Doenças do Desenvolvimento Ósseo/diagnóstico por imagem , Doenças do Desenvolvimento Ósseo/genética , Cromossomos Humanos Par 14/genética , Cromossomos em Anel , Ultrassonografia Pré-Natal , Anormalidades Múltiplas/diagnóstico por imagem , Adulto , Líquido Amniótico/química , Doenças do Desenvolvimento Ósseo/embriologia , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Idade Gestacional , Humanos , Cariotipagem , Linfangioma Cístico/diagnóstico por imagem , Masculino , GravidezRESUMO
BACKGROUND: Homogeneous and complete trisomy 8 is extremely rare. With one recent neonatal exception, all reported cases have been mosaic, due to mitotic non-disjunction during early zygotic development. We report a case of chromosome 8 trisomy in a human embryo examined at Carnegie stage 11 (25 days post-fertilization). It presented severe cardiovascular and central nervous system malformations. METHODS: The unusual bifid heart in this embryo spurred a detailed histological examination, karyotyping of a chorionic villus sample and subsequent FISH on inter-phase nuclei of intra-embryonic sections. RESULTS: Trophoblast cells had a karyotype of 47,XX, +8. Within the embryo proper, FISH demonstrated that the trisomy 8 was homogeneous in embryonic as well as extra-embryonic tissues. FQ-PCR supports a meiosis I origin of non-disjunction. In sections, the pharyngeal arches (including cardiac outflow tract), forebrain, mesonephros and liver were absent. Somites and yolk sac blood vessels were irregularly shaped. CONCLUSION: We show that homogeneous, intra-embryonic trisomy 8 is compatible with implantation and early human development. Molecular pathways that may be compromised and their impact on organogenesis are discussed.