Genetic Analysis To 2 Pedigrees With Wolf-Hirschhorn Syndrome And 5 Patients With Blepharophimosis-ptosis-epicanthus Inversus Syndrome

â… .Genetic analysis to 2 pedigrees with Wolf-Hirschhorn syndromeObjective:In order to investigate the origin of partial monosomy and trisomy 4p,search for genotype-phenotype correlations,and supply accurate diagnosis and genetic counselling to the patients and their families,genetic analysis was performed to two pedigrees with Wolf-Hirschhorn syndrome.Methods:Karyotyping,fluorescent in situ hybridization(FISH), whole genome copy number analysis using SNP array were performed to some members of the two pedigrees.Results:It was found that the proband and his younger sister in pedigree 1 were patients of Wolf-Hirschhorn syndrome,who carried a 2,767,380-bp(nt.63508-2830888) terminal deletion in chromosome 4p. The mother of proband was the carrier of t(4;14)(p16.3;p12) balanced translocation.In pedigree 2,the proband was patient of WHS,whose younger brother and uncle were patients of partial trisomy 4p,and the deletion and duplication sizes were about 5,047,291-bp(nt.64983-5112274).The proband of her father and grandmother were the carrier of t(4;15)(p16.2;p11.2) balanced translocation.Conclusions:In this study,we have made an accurate diagnosis to two pedigrees with Wolf-Hirschhorn syndrome using karyotyping, fluorescent in situ hybridization(FISH) and SNP array techniques. Definited the deletion and duplication size of chromosome 4p,refined the genotype-phenotype correlations:terminal deletion of 4p from 2.77Mb to 5Mb may include loci responsible for the Greek warrior helmet appearance and intrauterine growth retardation;there might be genes candidate for dental abnormalities and preauricular tags. â…¡.Genetic analysis to 5 patients with blepharophimosis-ptosis-epicanthus inversus syndromeObjective:To perform FOXL2 mutation analysis in 5 patients with blepharophimosis-ptosis-epicanthus inversus syndrome(BPES),refine the genotype-phenotype correlation,and supply accurate diagnosis and genetic counselling to the patients and their families.Methods:G-band karyotyping,fluorescent in situ hybridization (FISH),SNP array were performed to one patient with BPES and mental retardation,PCR and sequencing were performed to 4 only with BPES.Results:Patient 1 with mental retardation carried a 9.4 Mb heterozygous deletion in chromosome 3q22.1-q23 including FOXL2 gene. Both patient 2 and 3 carried a c.704delG heterozygous mutation of FOXL2,with clinical features of typeâ…¡BPES,while they were assigned to the different clinical type from those reported previously.No mutation of FOXL2 was detected in patient 4 and 5.Conclusions:(1) There might be the gene(s) responsible for mental retardation within chromosome 3q22.1-q23.(2) It was indicated that the mutation c.704delG in FOXL2 led to a truncated protein is associated with both typeâ… andâ…¡of BPES,therefore,the correlation of the genotype expressing truncated FOXL2 with the phenotype of premature ovarian failure in female patient with BPES typeâ… could not be established.