Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Genotypic and Phenotypic Spectrum of Foveal Hypoplasia: A Multicenter Study

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  1. Increased incidence of mental disorders in children with cataract - findings from a population-based study

    Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  2. Socio-economic status in families affected by childhood cataract

    Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  3. Long-term development of lens fluorescence in a twin cohort: Heritability and effects of age and lifestyle

    Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  4. Genetic disease is a common cause of bilateral childhood cataract in Denmark

    Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  • Helen J Kuht
  • Gail D E Maconachie
  • Jinu Han
  • Line Kessel
  • Maria M van Genderen
  • Rebecca J McLean
  • Michael Hisaund
  • Zhanhan Tu
  • Richard W Hertle
  • Karen Gronskov
  • Dayong Bai
  • Aihua Wei
  • Wei Li
  • Yonghong Jiao
  • Vasily Smirnov
  • Jae-Hwan Choi
  • Martin D Tobin
  • Viral Sheth
  • Ravi Purohit
  • Basu Dawar
  • Ayesha Girach
  • Sasha Strul
  • Laura May
  • Fred K Chen
  • Rachael C Heath Jeffery
  • Abdullah Aamir
  • Ronaldo Sano
  • Jing Jin
  • Brian P Brooks
  • Susanne Kohl
  • Benoit Arveiler
  • Lluis Montoliu
  • Elizabeth C Engle
  • Frank A Proudlock
  • Garima Nishad
  • Prateek Pani
  • Girish Varma
  • Irene Gottlob
  • Mervyn G Thomas
Vis graf over relationer

PURPOSE: To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH).

DESIGN: Multicenter, observational study.

PARTICIPANTS: A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384).

METHODS: Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans.

MAIN OUTCOME MEASURES: Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA).

RESULTS: The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH.

CONCLUSIONS: We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value.

OriginalsprogEngelsk
TidsskriftOphthalmology
Vol/bind129
Udgave nummer6
Sider (fra-til)708-718
Antal sider11
ISSN0161-6420
DOI
StatusUdgivet - jun. 2022

Bibliografisk note

Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

ID: 78193488