Genetic analysis of a Fra(16)(q22) fragile site in a female with secondary infertility / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Fra(16)(q22)/FRA16B fragile site in a female with secondary infertility.@*METHODS@#The 28-year-old patient was admitted to Chengdu Women's and Children's Central Hospital on October 5, 2021 due to secondary infertility. Peripheral blood sample was collected for G-banded karyotyping analysis, single nucleotide polymorphism array (SNP-array), quantitative fluorescent polymerase chain reaction (QF-PCR) and fluorescence in situ hybridization (FISH) assays.@*RESULTS@#The patient was found to harbor 5 mosaic karyotypes involving chromosome 16 in a total of 126 cells, which yielded a karyotype of mos 46,XX,Fra(16)(q22)[42]/46,XX,del(16)(q22)[4]/47,XX,del(16),+chtb(16)(q22-qter)[4]/46,XX,tr(16)(q22)[2]/46,XX[71]. No obvious abnormality was found by SNP-array, QF-PCR and FISH analysis.@*CONCLUSION@#A female patient with FRA16B was identified by genetic testing. Above finding has enabled genetic counseling of this patient.

Chromosomal microarray analysis of 17 patients with unbalanced reciprocal translocations / 中华医学遗传学杂志

OBJECTIVE@#To retrospectively analyze the results of chromosomal microarray analysis (CMA) and parental origins of unbalanced translocations among 17 patients, so as to provide reference for their genetic counseling.@*METHODS@#The results of CMA for 7 001 samples tested in Chengdu Women and Children's Central Hospital from January 2019 to January 2022 were retrospectively reviewed. Unbalanced reciprocal translocation was defined as two non-homologous chromosomes with lost and gained segments respectively or both with gained segments, and their parental origins were identified by parental chromosomal karyotyping and/or fluorescence in situ hybridization (FISH).@*RESULTS@#In total 17 unbalanced translocations were identified. In three cases, two non-homologous chromosomes both had gained segments, which constituted a derivative chromosome, with the total number of chromosomes being 47. In the remaining 14 cases, there was a terminal deletion on one chromosome and a terminal duplication on the other, 10 of which were confirmed by karyotyping, with the total number of chromosomes being 46. In the derivative chromosome, the lost segment was replaced by a gained segment from another chromosome. Among 15 cases undergoing parental origin analysis, 12 had paternal or maternal chromosomal abnormalities, including 11 balanced translocations and 1 unbalanced translocation. The unbalanced gametes therefore may form through meiosis. In 3 cases, the parental chromosomes were normal, indicating a de novo origin.@*CONCLUSION@#Discovery of terminal duplication and deletion or gained segments on two non-homologous chromosomes by CMA is suggestive of parental balanced translocation, which can facilitate genetic counseling and assessment the recurrence risk for subsequent pregnancies.

Prenatal diagnosis of 22q11.2 deletion syndrome in two consecutive pregnancies: a case report / 中华围产医学杂志

This article reports the prenatal diagnosis of 22q11.2 deletion syndrome (22q11.2 DS) in two consecutive pregnancies of a woman. Echocardiography on the first fetus at 24 +4 gestational weeks identified the right aortic arch, and right-sided ductus arteriosus with aberrant left subclavian artery. Subsequently, an amniocentesis was performed, and chromosomal microarray analysis (CMA) of amniotic fluid revealed a 2.181 Mb heterozygous microdeletion of 22q11.21, which indicated the presence of 22q11.2 DS in the fetus. After genetic counseling, the pregnant woman decided to terminate the pregnancy and declined genetic testing. During her second pregnancy, ultrasound at 21 +5 weeks detected interrupted aortic arch type B with aberrant left subclavian artery, ventricular septal defect, and enlarged posterior fossa in the fetus and further CMA of amniotic fluid indicated fetal 22q11.2 DS. CMA was performed on peripheral blood of the woman, which found the same deletion on 22q11.21. The woman had nasal sounds and velopharyngeal insufficiency with normal phenotype. Following the genetic counseling regarding the risk of recurrence, the pregnant woman opted to terminate the pregnancy and was suggested to undergo preimplantation genetic diagnosis in future pregnancies. One year after the second pregnancy termination, the woman's father developed heart failure at the age of 53 and was also found to have nasal sounds. Low-depth whole genome copy number variation sequencing in venous blood confirmed 22q11.2 DS in her father. For those with a prenatal diagnosis of 22q11.2 DS, genetic testing of the fetal parents is recommended to help assess the risk of recurrence and facilitate genetic counseling.