Maternal uniparental disomy 14 revealed by alpha 1 antitrypsin deficiency

摘要

Alpha 1 antitrypsin deficiency (AATD) is an autosomal co-dominant disease linked to a mutation of the SERPINA1 gene localized to chromosome 14q32. Uniparental disomy (UPD) is known to be a genetic mechanism that causes various syndromes. Maternal UPD14 presents with a Prader-Willi syndrome-like phenotype. No publications to date have dealt with the association of these two syndromes. In this article, we report on two cases of AATD (from different families), which lead to the diagnosis of maternal UPD14. AATD was diagnosed early in both children. Their clinical presentations were typical (chronic cytolysis in patient 1 and neonatal cholestasis in patient 2); serum alpha 1 antitrypsin levels were low (P1 0.33 g/L and P2 0.35 g/L), and both patients had a Z phenotype. A pedigree study of both families showed that the father had an M phenotype and the mother an MZ phenotype, which was unexpected. On the other hand, both children were born before term and presented with symmetrical growth retardation, early eating difficulties, moderate hypotonia, understated dysmorphic features and moderate psychomotor retardation, suggestive of a Prader-Willi syndrome-like phenotype. Genotyping was performed to explain gene transmission inconsistencies, and highlighted maternal UPD 14 in both families.