Genetic Analysis In 14 Cases With Product Of Concepts By Trio Whole
Exome Sequencing
Abstract
Objectives Whole exome sequencing technology can identify the
undiscovered genetic etiology of product of concepts(POC) and improve
the diagnosis rate of abortion.This study examines the value of a
combined trio-WES strategy in identifying the etiology of abortion in
the case of negative karyotype and chromosomal microarray sequencing.
Design: A retrospective study Setting: Center of Prenatal Diagnosis
Sample: Fourteen abortion samples with normal karyotype analysis and CMA
Methods: In this study, Trio-WES was used to sequence 14 POC with normal
CMA and karyotype analysis, and to evaluate the detection rate of
abnormal abnormalities and the diagnostic value of variation. Main
outcome measures: The detection rate of gene mutation sequence in flow
products, the definite diagnosis rate of single gene disease and its
relationship with clinical phenotype Results A total of 10 variants of 7
genes were detected, including 2 pathogenicity variant, 4 likely
pathogenicity variant and 4 uncertain significance variant. Four
families were accepted as positive results, with a definite diagnosis
rate of 28.6% (4/14). Case 1 was type 4 of autosomal dominant
polycystic kidney disease caused by complex heterozygous variation of
PKHD1 gene, Case 2 was Alagille syndrome caused by heterozygous
variation of JAG1 gene, Case 5 and Case7 were type 3 of short rib
dysplasia caused by complex heterozygous variation of DYNC2HI gene.
Conclusions These data support the application value of whole exome
sequencing technology in the detection of abortion etiology and enhance
the understanding of pathogenicity variation. Funding: National Key
Research and Development Program (2018YFC1002203-2);