Analysis of ANK1 gene mutation in a family with hereditary spherocytosis type Ⅰ / 中华医学遗传学杂志

Objective@#To detect the disease-causing mutation in a family with hereditary spherocytosis type Ⅰ.@*Methods@#Genomic DNA was extracted from peripheral blood samples of the proband and his relatives. Next-generation sequencing was used to detect the mutations of relevant genes. Suspected pathogenic mutation was verified by Sanger sequencing.@*Results@#The proband was found to harbor a novel frameshifting mutation in the coding region of ANK1 gene, which has resulted in abnormal structure or function of the protein. The mutation was confirmed by Sanger sequencing, with both his father and brother found to have carried the same mutation.@*Conclusion@#The c. 247delG mutation of proband hereditary spherocytosis typeⅠin this family due to mutation of the ANK1gene.

Genetic analysis of a Chinese family with congenital aniridia and detection of PAX6 mutation locus / 中华实验眼科杂志

Background Congenital aniridia is a rare bilateral hereditary ophthalmopathy which impact panocular.Researches showed that congenital aniridia can be caused by different mutation locus of PAX6 genes,and the mutations are multifarious.Objective This study was to detect and anaiyze the mutations of a Chinese family with congenital aniridia by using targeted sequence capture sequencing and direct Sanger sequencing.Methods This study was approved by Ethic Committee of the First Affiliated Hospital of Zhengzhou University and followed Declaration of Helsinki.Written informed consent was obtained from subjects or their custodians before any related medical examination.A cross-sectional study was performed.A Chinese congenital aniridia family was included at the First Affiliated Hospital of Zhengzhou University in March,2016.All the family members received systemic medical examinations including nervous system and oral glucose tolerance test and then the ocular examinations were carried out.The periphery blood of 10 ml was collected from the members for genomic DNA extraction.Targeted sequence capture sequencing was performed on the DNA of proband to screen out the suspicious mutant locus.The mutation was verified by comparing the Sanger direct sequencing results from all family members.Results A total of 3 generations of 9 members were included in this congenital aniridia pedigree,and the Ⅰ 1 was dead without eye abnormality.Three patients (Ⅱ2 and her children Ⅲ1,Ⅲ2) and 5 normal family members were determined,showing an autosomal dominant inheritance pattern.No abnormal signs were found in nervous system and oral glucose tolerance test in the families.The reduce of visual acuity,ocular hypertension (21 mmHg),absence of biocular iris,opacification of corneal stroma,horizontal nystagmus,hapoplasia of fovea were found in all the sufferers.In addition,the ptosis of the left eye,congenital cataract of the right eye in Ⅱ 2 patient as well as biocular cataract and subluxation of lenses also were exhibited.The c.183C＞A mutation of the PAX6 gene was screened out to be a possible pathogenic mutation.The result of Sanger direct sequencing in the families verified a co-segregation of this mutation with mutant phenotypes.Conclusions PAX6 gene c.183C ＞A,a rare mutation in Chinese population,is a virulence mutation site in this aniridia family.