The Etiopathogenisis Analysis And Prenatal Testing Of A Piebaldism Family The Etiopathogenisis Analysis Of A Hereditay Multiple Exostose

1.The etiopathogenisis analysis and prenatal testing of a piebaldism familyBackground:Piebaldism is a rare genetic disorder of the development of melanocytes. Piebaldism is an autosomal dominantly inherited disorder characterized by congenital white patches of skin.Depigmented areas are mainly found on the scalp,forehead,trunk and limbs.The leukoderma is usually stable throughout life.Heterozygous mutations in the KIT gene have been demonstrated in about 75% of patients with piebaldism.Objective We collected a piebaldism family of which three generations had been affacted. The family has 14 members,6 of them have severe phenotype.Two sisters of the proband are patients,each of them has an affected offspring.The proband have suffered artificial abortion 7 times,because she is afraid of having a similar child. The molecular genetics analysis was performed in the family to find the disease-causing mutation, and make the prenatal diagnosis available for the affected family members.Methods Ploymerase chain reaction(PCR), reverse transcription PCR and DNA sequencing were used to detect the mutation of KIT gene.Results We found a novel heterozygous mutation c.2472+1G>A in KIT gene of proband, which has not been reported and result in the loss of 3' splicing site and then absence of 17 exon in mRNA. The mutation was found in all affected members, while not in the unaffected ones of the family.Conclusion (1)The novel mutation c.2472+1 G>A is the disease-causing mutation in the piebaldism family.(2) The fetus of proband hasn't inheriting the mutation KIT allele of the family.2. The etiopathogenisis analysis of a hereditay multiple exostoseBackground:Hereditay multiple exostoses (HME) is an autosomal dominant condition characterized by the development of multiple exostoses from the metaepiphyseal areas of the long bones.The disorder usually involves the bones of the skeleton symmetrically,most commonly involved bones are the humerus,forearm and the bones about the knee and ankle. The exostoses vary widely in size and mumber, they can be present at birth and continue to appear and grow throughout childhood and into puberty.HME is genetically heterogeneous.The predominant relate-genes include EXT1 and EXT2.Objective The molecular genetics analysis was performed in a hereditay multiple exostose(HME) family.The disease was inherited three generations in the family,4 persons were affacted. Because apparente heredity traits of the disease,the proband's daughter was not dare to pregnant.Genetics test was performed to find the disease-causing mutation for providing genetic counseling and prenatal diagosis for the family members.Methods Ploymerase chain reaction and DNA sequencing were used to detect the muation of EXT1 and EXT2 genes,while denaturing high-performance liquid chormatography was performed to screen the mutation.Results We found a novel heterozygous deletion mutation c.2009-2012del(TCAA) in EXT1 gene of patients,which resulted in forming a lopping protein.The mutation was found in the else affected family members,and didn't find in the 50 unrelated normal individuals,which was unreported before.Conclusion (1)The novel mutation c.2009-2012del(TCAA) is the disease-causing mutation in the HME family. (2) The memberâ…¢3 of the family has the same mutation c.2009-2012del(TCAA),.We have a conclusion that she is a patient of HME.