Genetic analysis of a fetus with mosaic trisomy 12 and severe heart defects and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with severe heart defect and mosaic trisomy 12, and the correlation between chromosomal abnormalities and clinical manifestations and pregnancy outcome.@*METHODS@#A 33-year-old pregnant woman who presented at Lianyungang Maternal and Child Health Care Hospital on May 17, 2021 due to abnormal fetal heart development revealed by ultrasonography was selected as the study subject. Clinical data of the fetus were collected. Amniotic fluid sample of the pregnant women was collected and subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). The CNKI, WanFang and PubMed databases were searched with key words, with the retrieval period set as from June 1, 1992 to June 1, 2022.@*RESULTS@#For the 33-year-old pregnant woman, ultrasonography at 22+6 gestational weeks had revealed abnormal fetal heart development and ectopic pulmonary vein drainage. G-banded karyotyping showed that the fetus has a karyotype of mos 47,XX,+12[1]/46,XX[73], with the mosaicism rate being 1.35%. CMA results suggested that about 18% of fetal chromosome 12 was trisomic. A newborn was delivered at 39 weeks of gestation. Follow-up confirmed severe congenital heart disease, small head circumference, low-set ears and auricular deformity. The infant had died 3 months later. The database search has retrieved 9 reports. Literature review suggested that the liveborn infants with mosaic trisomy 12 had diverse clinical manifestations depending on the affected organs, which had included congenital heart disease and/or other organs and facial dysmorphisms, resulting in adverse pregnancy outcomes.@*CONCLUSION@#Trisomy 12 mosaicism is an important factor for severe heart defects. The results of ultrasound examination have important value for evaluating the prognosis of the affected fetuses.

Application of chromosomal microarray analysis in prenatal diagnosis of pregnant women with advanced age / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) for the detection of fetal anomalies among pregnant women with advanced age.@*METHODS@#CMA results of 562 cases, in addition with the outcome of pregnancy and neonatal follow-up were reviewed.@*RESULTS@#Among the 562 amniotic fluid samples, 73 cases (12.99%) of fetal chromosomal abnormalities were detected, which included 21 cases (3.73%) of chromosomal aneuploidies and 52 cases (9.25%) of copy number variations (CNVs). The latters included 27 cases of pathological CNVs (4.80%), 4 cases of possible pathogenic CNVs (0.71%) and 42 cases of variants with unknown clinical significance (7.47%). Compared with those under 35, the detection rate of fetal chromosomal aneuploidies for women with advanced age was higher under the indications of voluntary test, abnormal ultrasonic structures, abnormal ultrasonic soft index and risks indicated by non-invasive prenatal testing (NIPT). No significant difference was found in the detection rate of CNVs between those ≥35 and 0.05). 552 cases (98.22%) of pregnant women have completed the followed up. Among 31 women with pathological and possible pathogenic fetal CNVs detected by CMA, 25 had terminated the pregnancy, 6 (19.35%) have delivered without obvious abnormality. 41 pregnant women with fetal CNVs of unknown clinical significance have completed the follow up, among whom 3 had terminated the pregnancy, 1 newborn was found with malformation after birth, which yielded an abnormal pregnancy rate of 9.76%. 480 pregnant women with negative CMA results have completed the follow up, among whom 5 (1.04%) had abnormal pregnancy or delivered a child with birth defect.@*CONCLUSION@#There is a certain difference between the outcome of pregnancy predicted by CMA testing and the actual outcome. The pregnancies with fetal CNVs with unknown clinical significance detected by CMA have a high adverse rate, which should attract clinical attention. CMA testing should be recommended for pregnant women with advanced age regardless of whether they have other symptoms. CMA combined with other detection methods is the trend for prenatal diagnosis.

Analysis of clinical characteristics and related gene mutation characteristics in a case of maple syrup urine disease / 中华实用儿科临床杂志

The clinical characteristics and gene mutation characteristics of a child with typical maple syrup urine disease were analyzed retrospectively.The child is a boy, who showed unexplained milk refusal, poor reaction, foaming at the mouth, and encephalopathy symptoms 7 days after birth.The total leucine concentration was abnormally increased by blood tandem mass spectrometry, and the results of urine gas chromatography/mass spectrometry suggested that the concentrations of 2-hydroxy isovaleric acid, 2-keto isovaleric acid, 2-keto-3-methylpentanoic acid and 2-keto-isohexanoic acid were significantly increased.The gene detection results showed that c. 1028delC (p.S343Lfs*9) homozygous mutation was found in the BCKDHB gene.Understanding the clinical symptoms and gene mutation characteristics of this disease can help with the early detection and early diagnosis of this disease, so as to improve its prognosis to the greatest extent.

Genetic analysis of a case of mosaic trisomy 21 associated with autism spectrum disorder / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with autism spectrum disorder (ASD) and congenital heart disease.@*METHODS@#G-banded chromosomal karyotyping was carried out for the patient and his parents. The child was also subjected to whole exome sequencing (WES) and low-coverage massively parallel copy number variation sequencing (CNV-seq). The result was validated by chromosomal microarray analysis (CMA).@*RESULTS@#The karyotype of the patient and his parents were normal. No significant genetic variation was found by WES. However, CNV-seq has discovered a 47, XY, +21 [10%]/46,XY [90%] mosaicism in the patient. The result was confirmed by CMA.@*CONCLUSION@#In addition to Down syndrome, low proportion mosaic trisomy 21 is also associated with ASD. WES and CNV-seq can enable accurate diagnosis for patient with unexplained ASD.

Mutational analysis of 117 patients with non-syndromic hearing loss / 中华医学遗传学杂志

OBJECTIVE@#To determine the frequencies of deafness gene mutations among patients with non-syndromic hearing loss (NSHL) from northern Jiangsu province.@*METHODS@#A total of 117 patients with NSHL were enrolled. The coding region of GJB2 gene, IVS7-2A>G and 2168A>G mutations of SLC26A4 gene, and 1555A>G and 1494C>T mutations of mitochondrial DNA 12S rRNA were subjected to Sanger sequencing. Patients in whom no mutation was detected were further tested by targeted gene capture and high-throughput sequencing.@*RESULTS@#Among the 117 patients, 86 (73.50%) were found to carry mutations. GJB2 gene mutations were found in 61 patients (52.14%), including 22 (18.80%) with homozygous mutations and 39 (33.33%) with heterozygous mutations. SLC26A4 gene mutations were found in 19 patients (16.24%), including 4 (3.42%) with homozygous mutations and 15 with heterozygous mutations (14.53%). Mitochondrial 12S rRNA gene mutation was found in 6 patients (5.13%). Targeted gene capture and high-throughput sequencing of 8 patients identified 4 further cases, including 1 with RDX gene 129_130del and 76_79del compound heterozygous mutations, 1 with OTOF gene 1274G>C homozygous mutation, 1 with SLC26A4 gene 919-2A>G and IVS16-6G>A compound heterozygous mutation, and 1 with SLC26A4 gene 919-2A>G and A1673T compound heterozygous mutation.@*CONCLUSION@#The frequency of mutation among patients with NSHL from north Jiangsu was 73.50%, and GJB2 gene was most commonly mutated.