Mutation In The FOXL2 Gene And Clinical Characteristics In A Chinese Family With Blepharophimosis-ptosis-epicanthus Inversus Syndrome(BPES)

Objective: Blephrophimosis-ptosis-epicanthus inversus syndrome?BPES?is a rare autosomal dominant genetic disease.The distinctive syndrome has typical features,inc luding blephrarophimosis,optosis,epicanthus inversus and telecanthus.it is combine strabismus and refractive error,forming amblyopia and causing visual developmental disorders.This study examined the pathogenic genes of a fourth-generation Chinese B PES family and analyzed their clinical characteristics,providing a research basis for e lucidating the molecular genetic mechanism of the disease and developing genetic cou nseling.Methods: An autosomal dominant BPES family were recruited in the study.Th e clinical data of patients and normal members of the family were collected.The pa rticipants were inquired and recorded clinical medical history data,draw family maps,and improve related eye examinations,including eye photography,visual acuity,re fraction,the length and height of palpebral fissure,inner canthic diameter,the functio n of levator muscle of upper eyelid and frontal muscle.Collect 5 ml of peripheral v enous blood from patients and their family members and extract genomic DNA.For BPES patients,target sequence capture sequencing technology was used to genetic tes ting,then determine the pathogenic mutation site by Sanger sequencing and co-segreg ation verification.The pathogenic genes and mutation sites were determined.Accordin g to the American College of Medical Genetics and Genomics?ACMG?to evalue ge netic variation.Results :There were 104 people in the four generations of the family,including29 patients.Twenty-one patients were included in the study,including 13 patients a nd 8 normal family members.The average length of BPES is 23.1mm?17-28mm?in t he right eye and 22.7mm?13-26mm?in the left eye;the average height of palpebral fissure is 1.5mm?0.3mm-2mm?in the right eye and 2mm?1-3mm?in the left eye,t he average inner canthic diameter is 42mm?40-44mm?,the average function of levator muscle of upper eyelid of both eyes is 0mm?0-1mm?,the average function of fr ontal muscle of both eyes is 8.5mm?4-13mm?,and all patients are severe ptosis,nor mal intelligence,female patients were normal fertility.The refractive status of 8 patie nts?16 eyes?in the family was investigated.All 8 patients were accompanied by am blyopia.Gene test results showed that the FOXL2 gene of proband IV: 34 and patien t III: 32 was exon c.672₇01insGCGGCTGCCGCCGCAGCTGCTGCAGGCGCT?p.Al a234_Gly235insAAAAAAAAGA?heterozygous insertion mutation in 13 patients.None of these mutations were found in BPES patients and 100 unrelated healthy subjects.This mutation resulted in the insertion of 10 amino acids into the encoded polyalani ne chain,which increased the number of original polyalanine chains from 14 to 24,r esulting in an extended protein.The mutations determined according to the ACMG g enetic variation classification criteria and guidelines were determined to be pathogenic mutations that caused the onset of the family.Conclusions: The patients with BPES? detected FOXL2 gene heterozygous inser tion mutation c.672₇01insGCGGCTGCCGCCGCAGCTGCTGCAGGCGCT?p.Ala234_Gly235insAAAAAAAAGA?.This study expanded the gene mutation spectrum of the FOXL2 gene in the Chinese Han population,and provided a basis for elucidating the pathogenesis of BPES and genetic counseling.