Objective To investigate the clinical characteristics and perform the genetic analysis of a child of Noonan syndrome type 10(NS10).Methods The child and parents underwent trio-whole exome sequencing,and the variant was analyzed for harmfulness through bioinformatics.The protein structure function of variant was predicted,and western blot was conducted to analyze the expression level of variant protein.Results The patient was an 8-year-9-month-old boy with clinical manifestations including growth retardation,congenital heart disease,special face and so on.Genetic testing revealed a variant in leucine zipper like transcription regulator 1(LZTR1)gene,c.851G＞A(p.Arg284His)(NM_6767.4),which was inherited from his father,while his mother had the wild-type allele.This variant was new in LZTR1 gene,and there was no found in databases such as Pubmed and HGMD.SIFT,Polyphen-2 and MutationTaster online software analysis showed that LZTR1 c.851G＞A(p.Arg 284His)was biohazardous.The results of protein structure model analysis showed that LZTR1 c.851G＞A(p.Arg 284His)could lead to local structural changes of LZTR1 protein.Western blot results showed that the expression of variant-type LZTR1 protein was reduced by 81.20％compared with wild-type LZTR1 protein.Conclusions LZTR1 c.851G＞A(p.Arg 284His)may be a pathogenic factor for NS10.
Leucine zipper like transcription regulator 1Noonan syndromeGenetic testingTrio-whole exome sequencingWestern blot
万方数据
维普
