Correlation between FBN1 mutations and ocular features with ectopia lentis in the setting of Marfan syndrome and related fibrillinopathies

Mutations of fibrillin‐1 (FBN1) have been associated with Marfan syndrome and pleiotropic connective tissue disorders, collectively termed as “type I fibrillinopathy”. However, few genotype–phenotype correlations are known in the ocular system. Patients with congenital ectopia lentis (EL) received p...

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Bibliographic Details
Published in:Human mutation 2021-12, Vol.42 (12), p.1637-1647
Main Authors: Chen, Ze‐Xu, Chen, Tian‐Hui, Zhang, Min, Chen, Jia‐Hui, Lan, Li‐Na, Deng, Michael, Zheng, Jia‐Lei, Jiang, Yong‐Xiang
Format: Article
Language:English
Subjects:
axial length
Codons
Connective tissues
Cornea
ectopia lentis
Ectopia Lentis - genetics
Eye
FBN1
Fibrillin
Fibrillin-1 - genetics
Fibrillins - genetics
Genotype
Genotypes
genotype–phenotype analysis
Humans
Marfan syndrome
Marfan Syndrome - complications
Marfan Syndrome - diagnosis
Marfan Syndrome - genetics
Marfan's syndrome
Microfilament Proteins - genetics
Mutation
Neonates
Phenotype
Phenotypes
TGF‐β signaling
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Summary:Mutations of fibrillin‐1 (FBN1) have been associated with Marfan syndrome and pleiotropic connective tissue disorders, collectively termed as “type I fibrillinopathy”. However, few genotype–phenotype correlations are known in the ocular system. Patients with congenital ectopia lentis (EL) received panel‐based next‐generation sequencing, complemented with multiplex ligation‐dependent probe amplification. In a total of 125 probands, the ocular phenotypes were compared for different types of FBN1 mutations. Premature termination codons were associated with less severe EL and a thinner central corneal thickness (CCT) than the inframe mutations. The eyes of patients with mutations in the C‐terminal region had a higher incidence of posterior staphyloma than those in the middle and N‐terminal regions. Mutations in the TGF‐β‐regulating sequence had larger horizontal corneal diameters (white‐to‐white [WTW]), higher incidence of posterior staphyloma, but less severe EL than those with mutations in other regions. Mutations in the neonatal region were associated with thinner CCT. Longer axial length (AL) was associated with mutations in the C‐terminal region or TGF‐β regulating sequence after adjusting for age, EL severity, and corneal curvature radius. FBN1 genotype–phenotype correlations were established for some ocular features, including EL severity, AL, WTW, CCT, and so forth, providing novel perspectives and directions for further mechanistic studies.
ISSN:1059-7794
1098-1004
DOI:10.1002/humu.24283