Details

Autor(en) / Beteiligte

• Olivier, Guillaume
• Corton, Marta
• Intartaglia, Daniela
• Verbakel, Sanne K
• Sergouniotis, Panagiotis I
• Le Meur, Guylène
• Dhaenens, Claire-Marie
• Naacke, Hélène
• Avila-Fernández, Almudena
• Hoyng, Carel B
• Klevering, Jeroen
• Bocquet, Béatrice
• Roubertie, Agathe
• Sénéchal, Audrey
• Banfi, Sandro
• Muller, Agnès
• Hamel, Christian L
• Black, Graeme C
• Conte, Ivan
• Roosing, Susanne
• Zanlonghi, Xavier
• Ayuso, Carmen
• Meunier, Isabelle
• Manes, Gaël

Titel

Pathogenic variants in IMPG1 cause autosomal dominant and autosomal recessive retinitis pigmentosa

Ist Teil von

• Journal of medical genetics, 2021-08, Vol.58 (8), p.570

Ort / Verlag

England

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Inherited retinal disorders are a clinically and genetically heterogeneous group of conditions and a major cause of visual impairment. Common disease subtypes include vitelliform macular dystrophy (VMD) and retinitis pigmentosa (RP). Despite the identification of over 90 genes associated with RP, conventional genetic testing fails to detect a molecular diagnosis in about one third of patients with RP. Exome sequencing was carried out for identifying the disease-causing gene in a family with autosomal dominant RP. Gene panel testing and exome sequencing were performed in 596 RP and VMD families to identified additional variants. In vivo analysis in the medaka fish system by knockdown assays was performed to screen possible pathogenic role. Exome sequencing of a family with RP revealed a splice variant in . Subsequently, the same variant was identified in individuals from two families with either RP or VMD. A retrospective study of patients with RP or VMD revealed eight additional families with different missense or nonsense variants in . In addition, the clinical diagnosis of the retinopathy-associated variant, originally described as benign concentric annular macular dystrophy, was also revised to RP with early macular involvement. Using morpholino-mediated ablation of and its paralog in medaka fish, we confirmed a phenotype consistent with that observed in the families, including a decreased length of rod and cone photoreceptor outer segments. This study discusses a previously unreported association between monoallelic or biallelic variants and RP. Notably, similar observations have been reported for .