Mild form of oculocutaneous albinism type 1: phenotypic analysis of compound heterozygous patients with the R402Q variant of the TYR gene
| Autor: | Jean-François Korobelnik, Xavier Zanlonghi, Dominique Bonneau, Benoit Arveiler, Caroline Rooryck-Thambo, Perrine Pennamen, Yaurama Perdomo, Vincent Michaud, Sabine Defoort-Dhellemmes, C. Paya, Hélène Dollfus, Fanny Morice-Picard, Christian P. Hamel, Claudio Plaisant, Solene Monfermé, Catherine Duncombe-Poulet, Eulalie Lasseaux, Isabelle Drumare |
|---|---|
| Přispěvatelé: | CHU Bordeaux [Bordeaux], Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Strasbourg, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Visual acuity Photophobia albinism Compound heterozygosity 0302 clinical medicine Child A/p.Arg402Gln) Aged 80 and over Monophenol Monooxygenase Middle Aged Oculocutaneous albinism Sensory Systems Hypoplasia Pedigree Phenotype Albinism Oculocutaneous Child Preschool Brown hair visual_art Albinism foveal hypoplasia Female medicine.symptom hypopigmentation nystagmus Adult medicine.medical_specialty Adolescent R402Q (c.1205G> genotype-phenotype correlation TYR gene Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience visual_art.color Ophthalmology medicine Humans Aged Retrospective Studies Hypopigmentation business.industry Infant Newborn Infant medicine.disease 030104 developmental biology Mutation 030221 ophthalmology & optometry business [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | British Journal of Ophthalmology British Journal of Ophthalmology, BMJ Publishing Group, 2019, 103 (9), pp.1239-1247. ⟨10.1136/bjophthalmol-2018-312729⟩ |
| ISSN: | 1468-2079 0007-1161 |
| DOI: | 10.1136/bjophthalmol-2018-312729 |
| Popis: | AimOculocutaneous albinism type 1 (OCA1) is due to TYR mutations. c.1205G>A/p.Arg402Gln (R402Q) is a thermosensitive variant of the TYR gene that has been reported to be responsible for mild forms of OCA1. The aim of our study was to define the phenotype associated with this variant.MethodsIn our retrospective series, among 268 patients diagnosed with OCA1, 122 (45.5%) harboured one pathogenic variant of TYR, and the R402Q variant ensured to be in trans by segregation analysis in 69 patients (25.7%), constituting the ‘R402Q-OCA1’ group. 146 patients harboured two pathogenic variants of the TYR gene other than R402Q. Clinical records were available for 119 of them, constituting the ‘Classical-OCA1’ group.ResultsMost R402Q-OCA1 patients presented with white or yellow-white hair at birth (71.43%), blond hair later (46.97%), a light phototype but with residual pigmentation (69.64%), and blue eyes (76.56%). Their pigmentation was significantly higher than in the classical-OCA1 group. All patients from the R402Q-OCA1 group presented with ocular features of albinism. However the prevalence of photophobia (78.13%) and iris transillumination (83.87%) and the severity scores of iris transillumination, retinal hypopigmentation and foveal hypoplasia were lower in the R402Q-OCA1 group. Visual acuity was higher in the R402Q-OCA1 group (0.38±0.21 logarithm of the minimum angle of resolution vs 0.76±0.24). Investigations concerning a possible additive effect of the c.575C>A/p.Ser192 (S192Y) variant of TYR in cis with R402Q, suggested by others, showed no significant impact on the phenotype.ConclusionThe R402Q variant leads to variable but generally mild forms of albinism whose less typical presentation may lead to underdiagnosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|