Mutational Analysis Of The KIF21A、PHOX2A、TUBB3, TUBB2B Gene In One Chinese CFEOM Pedigree And Some Sporadic Patients

Objective The study was conducted to discuss the heterogeneity of Chinese CFEOM person by analyzing the clinical phenotype and genetic features of one Chinese CFEOM family and some sporadic patients.Methods A Chinese CFEOM pedigree (pedigree JN) and seven sporadic patients who visited the Affiliated Hospital of Qingdao University were collected. One hundred normal persons with no consanguinity from the same place were used as controls. Ophthalmologic examinations were recorded to analysis clinical characteristic. Blood samples were gained from the family members, seven sporadic patients and100normal controls. DNA of the participants’peripheral blood leukocytes were extracted with the standard ways of protocol. Gene mutation detection in the previous known mutation area of KIF21A, ABIX/PHOX2A, TUBB3, and TUBB2B were performed by PCR amplification and sequence analysis.RESULTS1.Clinical characteristics:The patients in the CFEOM family had bilateral ptosis, chin lift and restricted eye movement. Among seven CFEOM sporadic patients, including5male,2female. Three patients were esotropia, two patients had abnormal innervation, one had Marcus-Gunn syndrome.2.Genetic characteristics:Two affected persons in pedigree JN harbored a missense mutation (286C＞T), while the mutation was not detected in the normal persons of the family and100normal controls. The previously known mutations of KIF21A、ARIX、TUBB3and TUBB2B in CFEOM were not found in the sporadic cases.CONCLUSIONS1.According to the clinical manifestation and genetic trait, this CFEOM family met to CFEOM1pedigree. Seven sporadic cases had various clinical manifestation, One met to CFEOM1, one met to CFEOM2, and others met to CFEOM3.2.In this study, 2860C＞T mutation of KIF21A resulted in pedigree JN. No mutations in the known areas of KIF21A,PHOX2A/ARIX,TUBB3,TUBB2B were found. In the sporadic cases We concluded that the main virulence gene in the7CFEOM sporadic patients were different from the hot mutations in other population, suggesting that heterogeneity exists in CFEOM.