title: Maternal uniparental disomy 14 revealed by alpha 1 antitrypsin deficiency.
abstract: 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 0.33g/L and P2 0.35g/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.
  
  
  CONCLUSIONS
  Logically, maternal UPD 14 can induce AATD. In light of these observations, it seems appropriate to search for AATD in patients with maternal UPD 14 in order to prevent a progression of the disease. These cases also underline the significance of maternal UPD 14, which should be suspected in AATD in view of the discordance with Mendel's allelic transmission law.
authors.affiliation: Service de gastroentérologie, hépatologie et nutrition pédiatrique, hôpital Femme-Mère-Enfant, hospices civils de Lyon, université Lyon 1, CHU de Lyon, 59, boulevard Pinel, 69500 Bron, France. Electronic address: noemie.laverdure@free.fr.
authors.forename: Noémie
authors.initials: N
authors.lastname: Laverdure
authors.affiliation: Service de pédiatrie, hôpital Sud, université Rennes 1, CHU de Rennes, 16, boulevard de Bulgarie, BP 90347, 35203 Rennes cedex, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Dabadie
authors.affiliation: Service de génétique clinique, hôpital Femme-Mère-Enfant, hospices civils de Lyon, université Lyon 1, CHU de Lyon, 59, boulevard Pinel, 69500 Bron, France.
authors.forename: Marie Pierre
authors.initials: MP
authors.lastname: Alex-Cordier
authors.affiliation: Service de génétique clinique, hôpital Sud, université Rennes 1, CHU de Rennes, 16, boulevard de Bulgarie, BP 90347, 35203 Rennes cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.affiliation: Service de gastroentérologie, hépatologie et nutrition pédiatrique, hôpital Femme-Mère-Enfant, hospices civils de Lyon, université Lyon 1, CHU de Lyon, 59, boulevard Pinel, 69500 Bron, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Lachaux
mesh_terms: D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009035:Mothers; D010375:Pedigree; D024182:Uniparental Disomy / Q000175:diagnosis*; D019896:alpha 1-Antitrypsin Deficiency / Q000209:etiology*