Thymic hypoplasia induced by copy number variations contributed to explaining sudden infant death based on forensic autopsies

Chuanxiang Chen; Cui Zhang; Yongjian Deng; Sihao Du; Huijun Wang; Dongri Li

doi:10.1016/j.forsciint.2022.111323

Thymic hypoplasia induced by copy number variations contributed to explaining sudden infant death based on forensic autopsies

Forensic Sci Int. 2022 Jul:336:111323. doi: 10.1016/j.forsciint.2022.111323. Epub 2022 May 2.

Authors

Chuanxiang Chen¹, Cui Zhang¹, Yongjian Deng², Sihao Du¹, Huijun Wang³, Dongri Li⁴

Affiliations

¹ School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China; Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China.
² Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
³ School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China; Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China; Department of Laboratory Medicine, The Seventh Affiliated Hospital Of Southern Medical University, Foshan, Guangdong 528244, China. Electronic address: hjwang@smu.edu.cn.
⁴ School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China; Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou 510515, China. Electronic address: lidongri@smu.edu.cn.

PMID: 35580511
DOI: 10.1016/j.forsciint.2022.111323

Abstract

Thymic hypoplasia is a primary cellular immunodeficiency that causes susceptibility to serious infections leading to sudden death in infants. Some genetic disorders in humans could result in the evident permanent hypoplasia or occasional aplasia of the thymus at birth. However, determining the genetic etiology of thymic hypoplasia is challenging for the sudden infant death due to primary cellular immunodeficiency. In this study, in order to find the fundamental reasons for sudden death of infants with thymic hypoplasia, 5 infants with suspected thymic hypoplasia and 10 control infants were assessed, and the immunohistochemistry and DNA analysis were used to investigate whether the infants with thymic hypoplasia had DiGeorge syndrome (DGS) with copy number variations (CNVs) in 22q11.2 and other chromosomes. The results showed that the weight of the thymus was significantly lower than the normal except the case 4, and that all the infants had hypocalcemia and a significant decrease or even absence of the markers CD1a, CD2, CD3, CD4 and CD8, which are related to T-cell maturation. In addition, multiplex ligation-dependent probe amplification (MLPA) analysis showed that these infants carried CNVs in 22q11.2 and other associated chromosomes with deletion and duplication of 25 genes. The results of thymus weight, histopathology, molecular pathology and MLPA analysis suggested that DGS predominantly with thymic hypoplasia induced by CNVs caused the sudden death of these infants under various infections or other unexplained reasons, which may provide new insights into the diagnosis of sudden infant death and could help the parents of deceased infants to attach more importance of genetic screening and thymus ultrasound to reduce the postnatal mortality of the infant, and demonstrates the value of genetic diagnosis in the forensic pathology.

Keywords: 22q11.2 deletion, DiGeorge syndrome, Forensic pathology; Immunohistochemical analysis; MLPA; Thymic hypoplasia.

MeSH terms

Autopsy
DNA Copy Number Variations
DiGeorge Syndrome* / genetics
DiGeorge Syndrome* / pathology
Humans
Infant
Infant, Newborn
Multiplex Polymerase Chain Reaction
Sudden Infant Death* / genetics