PMID- 33633439
OWN - NLM
STAT- MEDLINE
DCOM- 20211105
LR  - 20221207
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 27
DP  - 2021
TI  - Confirming and expanding the phenotypes of FZD5 variants: Coloboma, inferior 
      chorioretinal hypoplasia, and high myopia.
PG  - 50-60
AB  - PURPOSE: Two frameshift and two indel variants in FZD5 have been reported to 
      cause coloboma in two families with incomplete penetrance and in two isolated 
      cases in previous studies, respectively. This study aims to confirm this 
      association and expand related specific phenotypes based on the 
      genotype-phenotype analysis of FZD5 variants. METHODS: Variants in FZD5 were 
      collected from our in-house exome sequencing data of 5,845 probands with 
      different eye conditions. Multistep bioinformatics analysis was used to classify 
      the variants. Potential pathogenic variants and phenotypic variations were 
      further evaluated based on family segregation and genotype-phenotype analysis. 
      RESULTS: In total, 63 rare variants were detected in FZD5. Multistep 
      bioinformatics and genotype-phenotype analyses suggested that eight rare 
      heterozygous variants in nine families should be considered potential pathogenic 
      variants: three novel frameshift variants (c.350_356delCGCCGCT/p.Ser117*, 
      c.1403_1406dupACCT/p.Tyr470Profs*130, and c.1428delG/p.Ser477Alafs*130) and five 
      novel missense variants (c.388C>A/p.Arg130Ser, c.794G>T/p.Arg265Leu, 
      c.1162G>A/p.Gly388Ser, c.1232A>G/p.Tyr411Cys, and c.1510A>T/p.Met504Leu). Among 
      the nine families, carriers of these variants showed overlapping phenotypes, 
      including typical uveal coloboma (12 eyes of seven patients from four families), 
      inferior chorioretinal hypoplasia (ICH) or optic disc hypoplasia (ODH; 12 eyes of 
      eight patients from six families), and high myopia (10 eyes of five patients from 
      five families) within individual families or among different families. 
      CONCLUSIONS: The data presented in this study confirmed that variants in FZD5, 
      not only frameshift variants but also missense variants, are a common cause of 
      uveal coloboma. In addition, ICH, ODH, and high myopia may be variant phenotypes 
      that are frequently associated with FZD5 variants.
CI  - Copyright (c) 2021 Molecular Vision.
FAU - Jiang, Yi
AU  - Jiang Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Ouyang, Jiamin
AU  - Ouyang J
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Li, Shiqiang
AU  - Li S
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Xiao, Xueshan
AU  - Xiao X
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Sun, Wenmin
AU  - Sun W
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Zhang, Qingjiong
AU  - Zhang Q
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210120
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (FZD5 protein, human)
RN  - 0 (Frizzled Receptors)
SB  - IM
MH  - Adult
MH  - Child
MH  - Child, Preschool
MH  - Choroid/*abnormalities
MH  - Coloboma/diagnosis/*genetics
MH  - DNA Mutational Analysis
MH  - Female
MH  - Frameshift Mutation/*genetics
MH  - Frizzled Receptors/*genetics
MH  - Humans
MH  - Infant
MH  - Male
MH  - Microscopy, Acoustic
MH  - Middle Aged
MH  - Mutation, Missense/*genetics
MH  - Myopia, Degenerative/diagnosis/*genetics
MH  - Pedigree
MH  - Phenotype
MH  - Retina/*abnormalities
MH  - Slit Lamp Microscopy
MH  - Exome Sequencing
MH  - Young Adult
PMC - PMC7883931
EDAT- 2021/02/27 06:00
MHDA- 2021/11/06 06:00
PMCR- 2021/01/01
CRDT- 2021/02/26 06:02
PHST- 2020/10/09 00:00 [received]
PHST- 2021/01/18 00:00 [accepted]
PHST- 2021/02/26 06:02 [entrez]
PHST- 2021/02/27 06:00 [pubmed]
PHST- 2021/11/06 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 5 [pii]
PST - epublish
SO  - Mol Vis. 2021 Jan 20;27:50-60. eCollection 2021.