PMID- 37225827
OWN - NLM
STAT- MEDLINE
DCOM- 20231207
LR  - 20240126
IS  - 1476-5454 (Electronic)
IS  - 0950-222X (Print)
IS  - 0950-222X (Linking)
VI  - 37
IP  - 18
DP  - 2023 Dec
TI  - Deep phenotypic characterization of the retinal dystrophy in patients with 
      RNU4ATAC-associated Roifman syndrome.
PG  - 3734-3742
LID - 10.1038/s41433-023-02581-1 [doi]
AB  - PURPOSE: To characterize the retinal phenotype in RNU4ATAC-associated Roifman 
      syndrome. METHODS: Ten patients (including 8 males) with molecularly confirmed 
      Roifman syndrome underwent detailed ophthalmologic evaluation including fundus 
      imaging, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence 
      tomography (SD-OCT), and electroretinography (ERG). Six patients had follow-up 
      eye exams. All patients also underwent comprehensive examination for features of 
      extra-retinal Roifman syndrome. RESULTS: All patients had biallelic RNU4ATAC 
      variants. Nyctalopia was common (7/10). Visual acuity at presentation ranged from 
      20/20 to 20/200 (Age Range: 5-41 years). Retinal exam revealed features of 
      generalized retinopathy with mid-peripheral pigment epithelial changes. A para or 
      peri-foveal ring of hyper-autofluorescence was the commonest FAF abnormality 
      noted (6/8). The SD-OCT demonstrated relative preservation of the foveal 
      ellipsoid zone in six cases; associated features included cystoid changes (5/10) 
      and posterior staphyloma (3/10). The ERG was abnormal in all patients; nine 
      showed generalized rod-cone dystrophy, whilst one patient with sectoral retinal 
      involvement only had isolated rod dystrophy (20 years old). On follow-up 
      examination (Mean duration: 8.16 years), progressive loss of visual acuity (2/6), 
      mid-peripheral retinal atrophy (3/6) or shortening of ellipsoid zone width (1/6) 
      were observed. CONCLUSION: This study has characterized the retinal phenotype in 
      RNU4ATAC-associated Roifman syndrome. Retinal involvement is universal, 
      early-onset, and overall, the retinal and FAF features are consistent with 
      rod-cone degeneration that is slowly progressive over time. The sub-foveal 
      retinal ultrastructure is relatively preserved in majority of patients. 
      Phenotypic variability independent of age exists, and more study of allelic- and 
      sex-based determinants of disease severity are necessary.
CI  - (c) 2023. Crown.
FAU - Ballios, Brian G
AU  - Ballios BG
AD  - Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, 
      ON, Canada.
FAU - Mandola, Amarilla
AU  - Mandola A
AD  - Division of Immunology and Allergy, The Hospital for Sick Children and the 
      University of Toronto, Toronto, ON, Canada.
FAU - Tayyib, Alaa
AU  - Tayyib A
AD  - Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, 
      ON, Canada.
AD  - Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, 
      Toronto, ON, Canada.
FAU - Tumber, Anupreet
AU  - Tumber A
AD  - Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, 
      Toronto, ON, Canada.
FAU - Garkaby, Jenny
AU  - Garkaby J
AD  - Division of Immunology and Allergy, The Hospital for Sick Children and the 
      University of Toronto, Toronto, ON, Canada.
FAU - Vong, Linda
AU  - Vong L
AD  - The Canadian Centre for Primary Immunodeficiency and The Jeffrey Modell Research 
      Laboratory for the Diagnosis of Primary Immunodeficiency, The Hospital for Sick 
      Children, Toronto, ON, Canada.
FAU - Heon, Elise
AU  - Heon E
AUID- ORCID: 0000-0003-4143-9311
AD  - Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, 
      ON, Canada.
AD  - Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, 
      Toronto, ON, Canada.
FAU - Roifman, Chaim M
AU  - Roifman CM
AD  - Division of Immunology and Allergy, The Hospital for Sick Children and the 
      University of Toronto, Toronto, ON, Canada.
AD  - The Canadian Centre for Primary Immunodeficiency and The Jeffrey Modell Research 
      Laboratory for the Diagnosis of Primary Immunodeficiency, The Hospital for Sick 
      Children, Toronto, ON, Canada.
FAU - Vincent, Ajoy
AU  - Vincent A
AUID- ORCID: 0000-0001-6446-3846
AD  - Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, 
      ON, Canada. ajoy.vincent@sickkids.ca.
AD  - Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, 
      Toronto, ON, Canada. ajoy.vincent@sickkids.ca.
LA  - eng
GR  - CD-CL-0617-0727-HSC/Foundation Fighting Blindness (Foundation Fighting Blindness, 
      Inc.)/
PT  - Journal Article
DEP - 20230524
PL  - England
TA  - Eye (Lond)
JT  - Eye (London, England)
JID - 8703986
RN  - Roifman syndrome
SB  - IM
MH  - Male
MH  - Humans
MH  - Child, Preschool
MH  - Child
MH  - Adolescent
MH  - Young Adult
MH  - Adult
MH  - Retina
MH  - *Retinal Dystrophies/diagnosis/genetics
MH  - *Osteochondrodysplasias
MH  - Electroretinography
MH  - Phenotype
MH  - Tomography, Optical Coherence/methods
MH  - Fluorescein Angiography
PMC - PMC10697969
COIS- The authors declare no competing interests.
EDAT- 2023/05/25 01:07
MHDA- 2023/12/07 12:43
PMCR- 2024/12/01
CRDT- 2023/05/24 23:22
PHST- 2022/12/30 00:00 [received]
PHST- 2023/05/11 00:00 [accepted]
PHST- 2023/05/01 00:00 [revised]
PHST- 2024/12/01 00:00 [pmc-release]
PHST- 2023/12/07 12:43 [medline]
PHST- 2023/05/25 01:07 [pubmed]
PHST- 2023/05/24 23:22 [entrez]
AID - 10.1038/s41433-023-02581-1 [pii]
AID - 2581 [pii]
AID - 10.1038/s41433-023-02581-1 [doi]
PST - ppublish
SO  - Eye (Lond). 2023 Dec;37(18):3734-3742. doi: 10.1038/s41433-023-02581-1. Epub 2023 
      May 24.