title: Further delineation of eye manifestations in homozygous 15q13.3 microdeletions including TRPM1: a differential diagnosis of ceroid lipofuscinosis.
abstract: The 15q13.3 heterozygous microdeletion is a fairly common microdeletion syndrome with marked clinical variability and incomplete penetrance. The average size of the deletion, which comprises six genes including CHRNA7, is 1.5 Mb. CHRNA7 has been identified as the gene responsible for the neurological phenotype in this microdeletion syndrome. Only seven patients with a homozygous microdeletion that includes at least CHRNA7, and is inherited from both parents have been described in the literature. The aim of this study was to further describe the distinctive eye manifestations from the analysis in the three French patients diagnosed with the classical 1.5 Mb homozygous microdeletion. Patients' ages ranged from 30 months to 9 years, and included one sib pair. They all displayed a remarkably severe identifiable clinical phenotype that included congenital blindness and convulsive encephalopathy with inconstant abnormal movements. The ophthalmological examination revealed a lack of eye tracking, optic nerve pallor, an immature response with increased latencies with no response to the checkerboard stimulations at the visual evoked potential examination, and a distinctive retina dystrophy with a negative electroretinogram in which the "b" wave was smaller than the "a" wave after a dark adapted pupil and bright flash in all patients. Clear genotype-phenotype correlations emerged, showing that this eye phenotype was secondary to homozygous deletion of TRPM1, the gene responsible for autosomal recessive congenital stationary night blindness. The main differential diagnosis is ceroid lipofuscinosis.
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d'Enfants, CHU Dijon, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel-Paulet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Drumare
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Cuisset
authors.forename: Louis
authors.initials: L
authors.lastname: Vallée
authors.forename: Sabine
authors.initials: S
authors.lastname: Defoort
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bourgois
authors.forename: Philippe
authors.initials: P
authors.lastname: Pernes
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Cuvellier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Salima El
authors.initials: SE
authors.lastname: Chehadeh
authors.forename: Julien
authors.initials: J
authors.lastname: Thevenon
authors.forename: Patrick
authors.initials: P
authors.lastname: Callier
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
mesh_terms: D001766:Blindness / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D004596:Electroretinography; D005123:Eye / Q000473:pathology; D005124:Eye Abnormalities / Q000235:genetics; D015785:Eye Diseases, Hereditary / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D040181:Genetic Diseases, X-Linked / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D008297:Male; D009216:Myopia / Q000235:genetics; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics* / Q000473:pathology; D009755:Night Blindness / Q000235:genetics; D009900:Optic Nerve / Q000002:abnormalities; D058499:Retinal Dystrophies / Q000235:genetics; D012640:Seizures / Q000235:genetics* / Q000473:pathology; D050053:TRPM Cation Channels / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: C579167:Chrna7 protein, human; D050053:TRPM Cation Channels; C492059:TRPM1 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: TRPM1; electroretinogram; homozygous 15q13.3 deletion