A rare mosaic 22q11.2 microdeletion identified in a Chinese family with recurrent fetal conotruncal defects.

Weicheng Chen,Liqun Sun,Xiaodi Li,Guoying Huang,Wei Sheng

doi:10.1002/mgg3.847

Abstract

Background22q11 deletion syndrome (22qDS) is caused by deletion of chromosome region 22q11.2. However, mosaic cases with 22q11.2 deletion syndrome (22q11.2DS) are rarely reported.MethodsChromosomal microarray analysis (CMA) and fluorescence in situ hybridization fluorescence in situ hybridization (FISH) were performed to analyze the copy number alterations. Clinical examinations related to 22q11.2DS were performed on the carrier in this family.ResultsA healthy female in a Chinese family with a history of two pregnancies with conotruncal defects, one with pulmonary atresia (PA) and another with Tetralogy of Fallot (TOF) was recruited in this study. CMA revealed that the fetus with TOF has a microdeletion on the 22q11.2 locus, and his mother was further confirmed a somatic mosaicism of 22q11.2 microdeletion by interphase FISH. Somatic mosaic 22q11.2 deletion in the mother was validated in the metaphase lymphocytes. Clinical examinations related to 22q11.2DS showed that the mother had hypocalcemia and low percentages of CD4 + T helper cells. The family history of recurrent fetal conotruncal defects and genetic results demonstrated the inherited possibility of maternal germline mosaicism of the 22q11.2 microdeletion.ConclusionOur report was the first case in a Chinese family to present that a somatic and suspected gonadal mosaicism of the 22q11.2 microdeletion in female causes recurrent fetal conotruncal defects.

Highlights

After the woman was married to her present husband, she had two continuous fetuses with conotruncal defects: an ultrasound examination of the previous fetus (Figure1 III2) revealed pulmonary atresia (PA) (The general diagnosis was from the medical records which did not mention that whether the PA was with or without intact ventricular septum and ultrasound images were not obtained); the echocardiographic images of the other fetus (Figure1 III3) showed Tetralogy of Fallot (TOF) (Figure2) and right renal agenesis that was suggestive of multiple malformations
A Chromosomal microarray analysis (CMA) of the fetus with TOF revealed a microdeletion on the 22q11.2 locus
fluorescence in situ hybridization (FISH) was performed on this family and showed that the asymptomatic mother had hybridization (FISH) analysis of the interphase nucleated blood cells shows a deletion on 22q11.2 in the fetuses’ mother (a) and normal signals in the fetuses’ father (b) and fetuses’ grandparents (c, d); FISH

Summary

| INTRODUCTION

22q11.2 deletion syndrome (22q11.2DS) refers to a syndrome that results from deletion of the 22q11.2 region, affecting approximately one in every 4,000 to 6,000 newborns and one in every 1,000 unselected fetuses (Kruszka et al., 2017). We reported the first case, in China, of a somatic and suspected gonadal mosaic 22q11.2 deletion in a mother who caused recurrent fetal conotruncal defects in a family; one fetus had pulmonary atresia (PA), and another had TOF. This case has implications for genetic counseling for families with 22q11.2DS

| Ethical compliance

| RESULTS

| DISCUSSION

Results