The Mutation Analysis In One Family With Blepharophimosis-Ptosis-Epicanthus Syndrome And Mutation Screen Of P4HA2 In Tujia High-Myopia Patients

Part1.FOXL2 mutation analysis in one family with both types of blepharophimosis-ptosis-epicanthus inversus syndromePurpose:Our study aims to identify the candidate mutation in FOXL2 in a Chinese family with both types of blepharophimosis-ptosis-epicanthus inversus syndrome（BPES）Methods:Clinical data and genomic DNA were collected from a Chinese family with blepharophimosis-ptosis-epicanthus inversus syndrome,Seven members of the family were recruited in this study,including four affected and three unaffected.All coding exons and adjacent regions of FOXL2 were screened in one affected member to detect causative mutation by Sanger sequencing.The detected mutation would be further screened in available family members as well as 100 normal control chromosomes.Results:The patient Ⅱ:5 showed typical features of type Ⅱ BPES characterized by a narrowed horizontal palpehral aperture,ptosis,epicanthus inversus and telecanthus without premature ovarian failure（POF）,whereas all her three daughters（Ⅲ:1,Ⅲ:2,Ⅲ:3）were diagnosed with type I BPES,in which a complex eyelid malformation is accompanied with POF.A novel heterozygous mutation in FOXL2（c.844₈60dup17,p.His291Argfs*71）was found in the four affected members and was absent in other three unaffected members as well as 100 control chromosomes.Conclusions:A novel duplicate mutation（c.844₈60dupl7,p.His291Argfs*71）in FOXL2 was identified in a Chinese family with both types of BPES.Our findings expand the mutation spectrum of the FOXL2 gene and confirmed the intra-family phenotypic heterogeneity of BPES.Part2.Mutation screen of P4HA2 in Tujia high-myopia patientsPurpose:P4HA2 was identified as a novel causative gene for nonsyndromic high-myopia.Our study aims to investigate the mutation of P4HA2 in 288 Tujia high-myopia patients,and to expand the mutation spectrum of P4HA2.Methods:Clinical data and genomic DNA were collected from 288 patients with high-myopia,whose spherical error<-6.00 diopters and the axial length ≥26.00mm。All coding exons regions of P4HA2 were screened in patients to detect causative mutation by Sanger sequencing.The detected mutation would be further screened in 192 normal control chromosomes in the same district.Results:Four variations in the P4HA2 gene were found in 288 patients,three missense mutations（c.145C>A,C.1306-62C>T,c.82+22C>T）,one insertion mutation（c.179+16₁79+17 ins T）,only missense mutation c.145C>A were damaging predicted by Polyphen2.Conclusions:the mutation c.145C>Amay be the cause of the high-myopia,P4HA2 is associated with Tujia high-myopia and the mutation frequency is low as（1/288）.Our study expand the mutation spectrum of P4HA2.