title: Incomplete penetrance of biallelic ALDH1A3 mutations.
abstract: The formation of a properly shaped eye is a complex developmental event that requires the coordination of many induction processes and differentiation pathways. Microphthalmia and anophthalmia (MA) represent the most severe defects that can affect the ocular globe during embryonic development. When genetic, these ocular disorders exhibit large genetic heterogeneity and extreme variable expressivity. Around 20 monogenic diseases are known to be associated with MA as main phenotype and the penetrance of mutations is usually full in the patients. Some of these genes encode proteins involved in the vitamin A pathway, tightly regulated during eye development. One of those retinoic acid synthesis genes is ALDH1A3 and biallelic mutations in that gene have been recently found to lead to MA phenotype in patients. Interestingly, we report here the lack of ocular defect in a girl carrying the same homozygous mutation in the ALDH1A3 gene than the affected members of her family. Thus, this report brings new information for the phenotype-genotype correlation of ALDH1A3 mutations and raises important questions, especially in terms of genetic counselling given to the patients and their families. Furthermore, these data contribute to the more general understanding that we have for the complex genetic inheritance of these MA phenotypes.
authors.affiliation: Genetics Department, Purpan University Hospital, France; UDEAR, UMR 1056 Inserm - Université de Toulouse, FRE 3742 CNRS, Toulouse, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Plaisancié
authors.affiliation: Pediatric Ophthalmology Department, Picardie Jules Verne University, University Hospital, Amiens, France; Ophthalmology Department, Necker-Enfants Malades University Hospital, APHP, France; CNRS Unit FR3636, Paris V University, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Brémond-Gignac
authors.affiliation: Medical Genetics and Oncogenetics Department, University Hospital, Amiens, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Demeer
authors.affiliation: Genetics Department, Purpan University Hospital, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Gaston
authors.affiliation: Genetics Department, Robert-Debré University Hospital, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.affiliation: INSERM U781 and Genetics Department, Paris Descartes University, Paris, France.
authors.forename: Lucas
authors.initials: L
authors.lastname: Fares-Taie
authors.affiliation: INSERM U781 and Genetics Department, Paris Descartes University, Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Gerber
authors.affiliation: INSERM U781 and Genetics Department, Paris Descartes University, Paris, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Rozet
authors.affiliation: Genetics Department, Purpan University Hospital, France; UDEAR, UMR 1056 Inserm - Université de Toulouse, FRE 3742 CNRS, Toulouse, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Calvas
authors.affiliation: Genetics Department, Purpan University Hospital, France; UDEAR, UMR 1056 Inserm - Université de Toulouse, FRE 3742 CNRS, Toulouse, France. Electronic address: chassaing.n@chu-toulouse.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D000853:Anophthalmos / Q000235:genetics* / Q000473:pathology; D002648:Child; D005123:Eye / Q000254:growth & development / Q000473:pathology*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008850:Microphthalmos / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D014212:Tretinoin / Q000378:metabolism
chemical_list: D014212:Tretinoin; D000445:Aldehyde Oxidoreductases; C018699:aldehyde dehydrogenase (NAD(P)+)
keywords: ALDH1A3; Anophthalmia; Eye development; Incomplete penetrance; Microphthalmia