Extending the phenotypic spectrum of PRPF8, PRPH2, RP1 and RPGR, and the genotypic spectrum of early-onset severe retinal dystrophy

Orphanet Journal of Rare Diseases

Tryfon Rotsos¹  Naser Ali²  Elizabeth Yang²  Parampal S. Grewal²  Anthony G. Robson³  Michalis Georgiou³  Michel Michaelides³  Nikolas Pontikos³ 

[1] First Division of Ophthalmology, General Hospital of Athens, National and Kapodistrian University of Athens, Athens, Greece;Moorfields Eye Hospital, London, UK;UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, EC1V 9EL, London, UK;Moorfields Eye Hospital, London, UK;

关键词: PRPF8;    PRPH2;    RP1;    RPGR;    Early onset retinal dystrophy;    LCA;    Leber congenital amaurosis;    Childhood blindness;    Inherited retinal dystrophy;    Severe early childhood onset retinal dystrophy;    SECORD;    EOSRD;   

DOI  :  10.1186/s13023-021-01759-8

来源: Springer

【 摘 要 】

PurposeTo present the detailed retinal phenotype of patients with Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy (LCA/EOSRD) caused by sequence variants in four genes, either not (n = 1) or very rarely (n = 3) previously associated with the disease.MethodsRetrospective case series of LCA/EOSRD from four pedigrees. Chart review of clinical notes, multimodal retinal imaging, electrophysiology, and molecular genetic testing at a single tertiary referral center (Moorfields Eye Hospital, London, UK).ResultsThe mean age of presentation was 3 months of age, with disease onset in the first year of life in all cases. Molecular genetic testing revealed the following disease-causing variants: PRPF8 (heterozygous c.5804G > A), PRPH2 (homozygous c.620_627delinsTA, novel variant), RP1 (homozygous c.4147_4151delGGATT, novel variant) and RPGR (heterozygous c.1894_1897delGACA). PRPF8, PRPH2, and RP1 variants have very rarely been reported, either as unique cases or case reports, with limited clinical data presented. RPGR variants have not previously been associated with LCA/EOSRD. Clinical history and detailed retinal imaging are presented.ConclusionsThe reported cases extend the phenotypic spectrum of PRPF8-, PRPH2-, RP1-, and RPGR-associated disease, and the genotypic spectrum of LCA/EOSRD. The study highlights the importance of retinal and functional phenotyping, and the importance of specific genetic diagnosis to potential future therapy.

【 授权许可】

CC BY