PMID- 29217025
OWN - NLM
STAT- MEDLINE
DCOM- 20171226
LR  - 20171226
IS  - 1715-3360 (Electronic)
IS  - 0008-4182 (Linking)
VI  - 52
IP  - 6
DP  - 2017 Dec
TI  - Correlation of novel PAX6 gene abnormalities in aniridia and clinical 
      presentation.
PG  - 570-577
LID - S0008-4182(16)30943-7 [pii]
LID - 10.1016/j.jcjo.2017.04.006 [doi]
AB  - OBJECTIVE: To describe the clinical presentation and genotype of subjects with 
      aniridia with a particular focus on foveal hypoplasia. DESIGN: Prospective cohort 
      study. PARTICIPANTS: Thirty-three Canadian participants with aniridia and of 
      various ethnic backgrounds residing in British Columbia. METHODS: Full ophthalmic 
      examinations and posterior segment spectral domain-optical coherence tomography 
      (SD-OCT) imaging were performed. Foveal hypoplasia was graded independently by 2 
      staff ophthalmologists. PAX6 sequencing was performed and chromosomal 11p 
      anomalies investigated. Candidate gene and single-nucleotide polymorphism 
      sequencing in genes functionally related to PAX6 were also studied. RESULTS: Best 
      corrected visual acuities in the cohort ranged from 0.0 logMAR to no light 
      perception. Total absence of iris tissue was seen in the majority (42 of 66 
      eyes). In those in whom SD-OCT was possible, foveal hypoplasia was seen in the 
      majority (45 of 56 eyes, 80%). Molecular genetic defects involving PAX6 were 
      identified in 30 participants (91%), including 4 novel PAX6 mutations (Gly18Val; 
      Ser65ProfsX14; Met337ArgfsX18; Ser321CysfsX34) and 4 novel chromosome 11p 
      deletions inclusive of PAX6 or a known PAX6 regulatory region. CONCLUSIONS: The 
      number of PAX6 mutations associated with aniridia continues to increase. Variable 
      foveal architecture despite nearly identical anterior segment disease in 4 
      participants with an Ex9 ELP4-Ex4 DCDC1 deletion suggested that molecular cues 
      causing variation in disease in the posterior segment differ from those at play 
      in the anterior segment. Results in 3 patients without identifiable PAX6 
      mutations and a review of the literature suggest that such cases be described as 
      phenocopies rather than actual cases of the syndrome of aniridia.
CI  - Copyright (c) 2017. Published by Elsevier Inc.
FAU - Sannan, Naif S
AU  - Sannan NS
AD  - Department of Ophthalmology and Visual Sciences, University of British Columbia, 
      Vancouver, B.C.
FAU - Gregory-Evans, Cheryl Y
AU  - Gregory-Evans CY
AD  - Department of Ophthalmology and Visual Sciences, University of British Columbia, 
      Vancouver, B.C.
FAU - Lyons, Christopher J
AU  - Lyons CJ
AD  - Department of Ophthalmology and Visual Sciences, University of British Columbia, 
      Vancouver, B.C; Department of Ophthalmology, BC Children's Hospital, Vancouver, 
      B.C.
FAU - Lehman, Anna M
AU  - Lehman AM
AD  - Department of Medical Genetics, University of British Columbia, Vancouver, B.C.
FAU - Langlois, Sylvie
AU  - Langlois S
AD  - Department of Medical Genetics, University of British Columbia, Vancouver, B.C.
FAU - Warner, Simon J
AU  - Warner SJ
AD  - Department of Ophthalmology and Visual Sciences, University of British Columbia, 
      Vancouver, B.C.
FAU - Zakrzewski, Helen
AU  - Zakrzewski H
AD  - Cumming School of Medicine, University of Calgary, Calgary, Alta.
FAU - Gregory-Evans, Kevin
AU  - Gregory-Evans K
AD  - Department of Ophthalmology and Visual Sciences, University of British Columbia, 
      Vancouver, B.C. Electronic address: kge30@mail.ubc.ca.
LA  - eng
PT  - Journal Article
DEP - 20170706
PL  - England
TA  - Can J Ophthalmol
JT  - Canadian journal of ophthalmology. Journal canadien d'ophtalmologie
JID - 0045312
RN  - 0 (PAX6 Transcription Factor)
RN  - 0 (PAX6 protein, human)
RN  - Chromosome 11, deletion 11p
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aniridia/*diagnosis/*genetics
MH  - Child
MH  - Chromosome Deletion
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Cohort Studies
MH  - Female
MH  - Fovea Centralis/*abnormalities
MH  - Gene Amplification
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - PAX6 Transcription Factor/*genetics
MH  - Phenotype
MH  - *Polymorphism, Single Nucleotide
MH  - Prospective Studies
MH  - Real-Time Polymerase Chain Reaction
MH  - Tomography, Optical Coherence
MH  - Visual Acuity/physiology
MH  - Young Adult
EDAT- 2017/12/09 06:00
MHDA- 2017/12/27 06:00
CRDT- 2017/12/09 06:00
PHST- 2016/10/27 00:00 [received]
PHST- 2017/03/24 00:00 [revised]
PHST- 2017/04/05 00:00 [accepted]
PHST- 2017/12/09 06:00 [entrez]
PHST- 2017/12/09 06:00 [pubmed]
PHST- 2017/12/27 06:00 [medline]
AID - S0008-4182(16)30943-7 [pii]
AID - 10.1016/j.jcjo.2017.04.006 [doi]
PST - ppublish
SO  - Can J Ophthalmol. 2017 Dec;52(6):570-577. doi: 10.1016/j.jcjo.2017.04.006. Epub 
      2017 Jul 6.