Mutation analysis of the autosomal dominant Weill-Marchesani syndrome and genotype-phenotype review

Authors: Li Jie,  Xing Yasi,  Li Zhanrong,  Qin Fangyuan,  Dai Shuzhen

DOI: 10.3760/cma.j.issn.2095-0160.2018.07.006
Published 2018-07-10
Cite as Chin J Exp Ophthalmol, 2018,36(7): 514-518.

Abstract                              [Download PDF] [Read Full Text]


To screen the disease-causing genes in an autosomal dominant(AD)Weill-Marchesani syndrome (WMS) family from Henan province in China, and to analyze the relationship between genotypes and phenotypes of the AD WMS.


A family with suspected WMS was collected and studied in Henan Eye Hospital from September 2016 to July 2017.Clinical data and genomic DNA of the families were analyzed and genetic variations were screened by whole-exome sequencing (WES) The candidate genes related to ectopia lentis (FBN1, ADAMTSL2, ADAMTSL4, TGFBR2, CBS, ADAMTS10, ADAMTS17) were analyzed, and multiplex ligation dependent probe amplification (MLPA) was applied.Novel variants were further evaluated by sequencing 96 normal individuals.The previous reports with similar genetic characteristics were reviewed and the mutation types and clinical features were summarized.Written informed consent was obtained from the participants or their guardians before the collection of their venous blood and clinical data.Ethical approval was obtained from the Institutional Review Board of Henan Eye Institute.


The suspicious mutation of the c. 5260G>A was detected in exon 42 of the FBN1 by WES in this family, which was predicted to be pathogenic and cosegregated with the disease; the clinical futures of the patients in the family included proportionate short stature, brachydactyly, joint stiffness, and the ocular problems included microspherophakia, moderate myopia, secondary glaucoma.Four mutations of FBN1 that related to WMS were reported in previous literature, and three of them were located in 41-42 exons and the others were the deletion of exons 9-11.All patients had typical clinical features of microspherophakia, short stature, brachydactyly, joint stiffness.In addition, thick skin was common, heart defects were occasional, protuberant abdomen and umbilical hernia were rarely reported.


The affected members in this family are in according with the clinical and genetic diagnosis of WMS.A novel mutation (c.5260G>A) in FBN1 is discovered, which increases the spectrum of WMS mutation.The 41-42 exons of the FBN1 are hotspot of mutation in WMS.

Key words:

Weill-Marchesani syndrome; FBN1 gene; Whole-exome sequencing; Phenotype

Contributor Information

Li Jie
Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450003, China
Xing Yasi
Li Zhanrong
Qin Fangyuan
Dai Shuzhen
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