دانلودمقاله باموضوع بررسی سیستماتیک ژنوتیپ-فنوتیپ همبستگی در سندرم فریزر
در قالب pdf و در 9 اسلاید،قابل ویرایش، شامل:
موضوع به انگلیسی:Systematic Review of Genotype-Phenotype
Correlations in Frasier Syndrome
بخشی از متن:Introduction: Frasier syndrome (FS) is a rare inherited kidney disease caused by intron 9 splicing variants
of WT1. For wild-type WT1, 2 active splice donor sites in intron 9 cause a mixture of 2 essential transcripts
(with or without lysine-threonine-serine [þ/KTS or KTS]), and imbalance of the þKTS/KTS ratio results
in the development of FS. To date, 6 causative intron 9 variants have been identified; however, detailed
transcript analysis has not yet been conducted and the genotype-phenotype correlation also remains to be
elucidated.
Methods: We conducted an in vitro minigene splicing assay for 6 reported causative variants and in vivo
RNA sequencing to determine the þKTS/KTS ratio using patients’ samples. We also performed a systematic
review of reported FS cases with a description of the renal phenotype.
Results: The in vitro assay revealed that although all mutant alleles produced KTS transcripts only, the
wild-type allele produced both þKTS and KTS transcripts at a 1:1 ratio. In vivo RNA sequencing showed
that patients’ samples with all heterozygous variants produced similar ratios of þKTS to KTS
(1:3.21:3.5) and wild-type kidney showed almost a 1:1 ratio (1:0.85). A systematic review of 126 cases
clarified that the median age of developing ESKD was 16 years in all FS patients, and there were no
statistically significant differences between the genotypes or sex chromosome karyotypes in terms of the
renal survival period
