Gene Diagnosis Of Hereditary Hypotrichosis And Search For New Pathogenic Gene

Objective:(1)To study the clinical manifestations and genetic patterns of a hereditary hypotrichosis /woolly hair pedigree and to find new pathogenic genes.(2)To study the clinical manifestations of a hypotrichosis simplx family and a Bjornstad syndrome family and to identify the mutations of pathogenic genes.Methods:(1)Pathological examination was carried out in a family with hereditary hypotrichosis /woolly hair.The ultrastructure of hair was observed by scanning electron microscopy.Blood samples of the family were collected.The whole genome linkage analysis and haplotype analysis and sequencing were carried out to identify the new pathogenic gene.The function of the new genes was further studied in engineered cells.(2)Blood samples were collected from a pedigree with hypotrichosis simplx,and the second generation targeting sequencing and mutation site validation were carried out to identify the pathogenic gene mutation of the patient.(3)Blood samples were collected from a family with Bjornstad syndrome,and the second generation targeted sequencing and mutation site verification were performed to confirm the diagnosis of the child.Results:(1)We found that a new pathogenic gene associated with hereditary hypotrichosis /woolly hair pedigree was located on chromosome 2,which was a heterozygous missense mutation c.1939G>A(p.D647N)of ADAM17 gene.At the level of m RNA,ADAM17 expression increased in both wild and mutant plasmids,while the expression of TGFalpha and EGFR in wild and mutant plasmids remained almost unchanged.At the protein level,the expression of wild type and mutant ADAM17 increased,while the expression of TGFα in wild type and mutant plasmids almost had no change,while the expression of EGFR in wild type plasmids had no significant change,but decreased in mutant plasmids.(2)The mutation of pathogenic gene in child with hypotrichosis simplx was c.54+2T>A heterozygous mutation of SNRPE gene.(3)Two complex heterozygous mutations were found in BCS1 L gene in child with Bjornstad syndrome,namely a c.818 del C deletion mutation and a c.917 G > A missense mutation.Conclusions: We found a new pathogenic gene causing hereditary hypotrichosis/woolly hair,and identified mutations in a hypotrichosis simplx family and a Bjornstad syndrome family.