OBJECTIVE: To carry out pathological and genetic analyses on a fetus with intrauterine growth restriction and death during second trimester after induced abortion. METHODS: A fetus undergone induced abortion due to intrauterine growth restriction and death during second trimester at the the Seventh Affiliated Hospital of Sun Yat-Sen University in 2024 was selected as the study subject. Clinical data of the pregnancy were collected. DNA was extracted from tissues from the aborted fetus and peripheral blood samples from its parents. Chromosomal microarray analysis and whole exome sequencing were carried out. Candidate variants were verified by Sanger sequencing. Following abortion, routine autopsy and pathological analysis were conducted. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: KY-2025-334-01). RESULTS: The aborted fetus was a male and harbored compound heterozygous nonsense variants of the TH gene (c.457C>T/p.Arg153* and c.694C>T/p.Gln232*), for which both parents were heterozygous carriers. Autopsy and pathological analysis revealed that the fetus had pathological features including loose arrangement of myocardial fibers and congestion in the liver. CONCLUSION Biallelic null variants of the TH gene may cause heart failure by affecting the development of cardiovascular system, which in turn may lead to intrauterine death. This study has provided new clues for the molecular diagnosis of stillbirth and recurrent pregnancy loss.
Humans ; Female ; Pregnancy ; Male ; Heterozygote ; Codon, Nonsense/genetics* ; Fetal Growth Retardation/pathology* ; Adult ; Stillbirth/genetics*

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the analysis of 824 samples from miscarriage or stillbirth. METHODS: Copy number variations (CNVs) in the abortic chorionic villi or stillbirth tissues were detected by CMA. RESULTS: All specimens were successfully analyzed, among which 381 (46.2%) were diagnosed with chromosomal abnormalities, which included 312 (81.9%) numerical abnormalities, 66 (17.3%) structural abnormalities and 3 (0.8%) uniparental disomies. Among numerical chromosomal abnormalities, aneuploidies was most common (92.0%), with trisomy 16 and 45,X accounting for 41 (13.1%) and 63 (20.2%) of the cases, respectively. Among the 66 structural chromosomal aberrations, there were 26 (39.4%) CNVs duplications, 20 (30.3%) CNVs deletions, and 20 (30.3%) CNVs duplication and deletions. 33 CNVs were predicted as have a high chance to lead to a disease. CONCLUSION CMA is a reliable, robust, and high-resolution method for the analysis of miscarriage or stillbirth samples. Numerical aberrations, in particular chromosomal aneuploides, are the main cause for spontaneous abortions and stillbirths.
Abortion, Spontaneous ; genetics ; Chromosome Aberrations ; Chromosome Disorders ; diagnosis ; genetics ; DNA Copy Number Variations ; Female ; Humans ; Microarray Analysis ; Pregnancy ; Stillbirth ; genetics

OBJECTIVETo assess the value of array-based comparative genomic hybridization (array-CGH) for analyzing tissues derived from spontaneous abortion and stillbirth.

METHODSAgilent Human Genome CGH Microarray 4×44 K chip and Affymetrix Cytoscan 750 K Array were utilized to detect genome-wide copy number variations (CNV) in 43 fetuses with spontaneous abortion and stillbirth. All identified CNV were analyzed with references from Database of Genomic variants (DGV), database of DECIPHER, ISCA and OMIM, as well as comprehensive literature review to determine whether the identified CNVs were pathogenic. Parental DNA of two cases was also analyzed with the same arrays for pathogenic or unknown significant CNVs.

RESULTSAll of the 43 specimens were successfully analyzed. Clinically significant chromosomal aberrations were identified in 32 (74.4%) of the samples, which included 26 aneuploidies and 10 pathogenic CNV.

CONCLUSIONArray-CGH is a fast and effective method for analyzing tissues derived from spontaneous abortions and stillbirths which may be difficult to culture for karyotype analysis.

Abortion, Spontaneous ; diagnosis ; genetics ; Adult ; Chromosome Aberrations ; Comparative Genomic Hybridization ; methods ; DNA Copy Number Variations ; Female ; Fetus ; chemistry ; Humans ; Karyotyping ; Pregnancy ; Pregnancy Complications ; diagnosis ; genetics ; Stillbirth ; genetics ; Young Adult