Objective:To explore the characteristics of a fetus with chromosome 1p36 deletion syndrome and 3p26.3p25.2 duplication.Methods:A pregnant woman who had attended the Genetic Counseling Clinic of Linyi People′s Hospital on February 22, 2022 and her fetus were selected as the study subjects. Clinical data were collected. Chromosomal karyotyping, fluorescence in situ hybridization (FISH) and chromosomal microarray analysis (CMA) were carried out for the prenatal diagnosis. Result:Ultrasonography at 24th gestational week revealed that the fetus had ventricular septal defect, single umbilical artery, and slight widening of left lateral ventricle (12 mm). The woman was found to have a karyotype of 46, XX, t(1; 3)(p36.22; p25.2), and the result of FISH was t(1; 3)(3pter+, 1qter+ ; 1pter+, 3qter+ ). The fetus was found to have a karyotype of 46, X?, add(1)(p36), and CMA confirmed that it has a 9.0 Mb deletion at 1p36.33p36.22 and a 12.6 Mb duplication at 3p26.3p25.2. Combining the maternal karyotype, the molecular karyotype of the fetus was determined as 46, X?, der(1)t(1; 3)(p36.22; p25.2)mat.arr[hg19]1p36.33p36.22(849467_9882666)×1, 3p26.3p25.2(61892_12699607)×3, with the former known to be associated with 1p36 deletion syndrome.Conclusion:The fetus was diagnosed with 1p36 deletion syndrome, and its 1p36.33p36.22 deletion and 3p26.3p25.2 duplication had both derived from the balanced translocation carried by its mother.

Objective:To carry out invasive prenatal diagnosis for a fetus with ultrasound-indicated agenesis of corpus callosum and explore its genetic etiology.Methods:A pregnant woman presented at the Affiliated Hospital of Putian College on December 16, 2022 was selected as the study subject. Amniotic fluid and peripheral blood samples from the fetus and the couple were collected. Conventional G-banded chromosomal karyotyping was carried out, and whole-genome copy number variation analysis was performed using single nucleotide polymorphism microarray (SNP-array).Results:The karyotypes of the fetus and the couple were normal by the G-banding analysis. SNP-array analysis of the amniotic fluid sample revealed a 4.5 Mb microdeletion in the 18q21.2q21.31 region of the fetus. SNP-array analysis of peripheral blood samples from the couple did not find any abnormality.Conclusion:Through G-banded chromosomal karyotyping and SNP-array analysis, a fetus with 18q21.2q21.31 microdeletion was identified, which has conformed to the diagnosis of Pitt-Hopkins syndrome. Above finding has provided a basis for genetic counseling for the couple.

Objective:To explore the genetic basis for a patient with Disorders of sex development (DSD).Methods:A female patient who had presented at the Linyi People′s Hospital due to primary amenorrhea on April 6, 2022 was selected as the study subject. Conventional chromosomal karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), fluorescence quantitative PCR and Sanger sequencing were carried out for the patient. Results:The patient, a 14-year-old female, had featured short statue, multiple nevi, and primary amenorrhea. She was found to have a karyotype of 46, X, idic(Y)(p11.3)[59]/45, X[39]/47, X, idic(Y)(p11.3)×2[2]. The result of FISH assay was 46, X, der(Y).ish idic(Y)(p11.3)( SRY+ )[59]/45, X[39]/47, X, der(Y)×2.ish idic(Y)(p11.3)( SRY+ )[2]. That of CMA was arr[GRCh37](X)×1, (Y)×0-1, arr[GRCh37]Yp11.32(118552_472090)×1. The patient had no deletion in the AZF region of Y chromosome, and was negative for variant of SRY gene. Combining the above results, her molecular karyotype was determined as mos 46, X, idic(Y)(p11.32)[59]/45, X[39]/47, X, idic(Y)(p11.32)×2[2].ish 46, X, idic(Y)(p11.32)( DXZ1+, DYZ1+ +, DYZ3+ +, SRY+ )[59]/45, X( DXZ1+, DYZ1-, DYZ3-, SRY-)[39]/47, X, der(Y)×2.ish idic(Y)(p11.32)( DXZ1+, DYZ1+ +, DYZ3+ +, SRY+ )[2].arr[GRCh37](X)×1, (Y)×0-1, arr[GRCh37]Yp11.32(118552_472090)×1. The patient was diagnosed with mosaicism DSD with idic(Y)(p11.32). Conclusion:The abnormal mosaicism karyotype probably underlay the DSD in this patient.

Congenital heart disease (CHD) is one of the most common congenital malformations and a major cause of mortality among neonates and children. Conventional methods for the diagnosis of CHD have relied on clinical features and imaging findings. With the rapid development of genetic techniques, to identify the cause of CHD through genetic diagnosis has gained great significance for the early diagnosis, treatment, and prevention of CHD. However, currently there is still a lack of norms and standards for the genetic diagnosis of CHD. In view of this, experts from the relevant fields have formulated the present norm by integrating the latest research advances on CHD-related genes with the current clinical practice on the diagnosis and treatment of CHD and status quo of genetic diagnosis in China. The norm has been recommended by the Cardiology Section of the Chinese Medical Education Association, the Medical Genetics Branch and the Heart Group of Pediatric Surgery Branch of the Chinese Medical Association, which has formulated the procedures and norms of genetic testing, prenatal diagnosis, and genetic counseling for CHD, with an aim to provide reference for clinicians as the standards for the integrated diagnosis, early treatment, and prevention of CHD.

Dystrophinopathies caused by variants of DMD gene are a group of muscular diseases including Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy. With the advancement of genetic testing techniques and wider implementation of genetic screening, especially the expanded carrier screening, more and more individuals carrying DMD gene variants have been identified, whereas the genetic counseling capacity is relatively insufficient. Currently there is still a lack of professional norms for genetic counseling on dystrophinopathies. In this consensus, the main points to be covered in the pre- and post-test consultation have been discussed, with an aim to provide genetic counseling guidance for the disease diagnosis, treatment, and family reproduction.

Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease with a carrier frequency of 1/60 ~ 1/40, is characterized by severe clinical symptoms, high mortality rate, and expensive treatment costs. Carrier screening is of paramount importance to detect high-risk couples, and therefore to reduce the occurrence of SMA. In China, SMA carrier screening has become widespread, though there is still a lack of genetic counseling expertise. This article has focused on the current challenges for SMA carrier screening, including the screening methods, target population, screening procedures, and pre-/post-testing counseling. The aim is to standardize its application and counseling in the clinical practice.

α-thalassemia is a type of microcytic hypochromic anemia caused by variants of alpha-globin gene, and is one of the most common monogenic disorders in southern China. The population screening model based on hematologic phenotype has achieved great results in areas with high incidence of thalassemia. However, with the continuous decline of the cost of genetic testing and implementation of screening programs for thalassemia gene carriers, more variants in the alpha-globin gene have been discovered, which also brings great challenges to clinical genetic counseling. From the perspective of alpha-globin genetic analysis, this consensus has discussed the contents of pre- and post-test genetic counseling, with an aim to provide standardized guidance for clinicians.

Fetal structural anomalies and birth defects are primarily caused by genetic variants such as chromosomal number abnormalities, copy number variations (CNV), single nucleotide variants (SNV), and small insertions and deletions (indel). Whole-genome sequencing (WGS) based on next-generation sequencing (NGS) as an emerging technology for genetic disease diagnosis can detect the aforementioned types of variants. In recent years, high-depth WGS (> 30×) for prenatal diagnosis has also become available, and proved to be practical for unraveling the genetic etiology of fetal developmental abnormalities. To fascilitate clinical practice, test development and preliminary implementation of WGS for diagnosing fetal structural anomalies, we have formulated a consensus over the application of WGS in prenatal diagnosis by compiling previously published consensuses, guidelines, and research findings to provide a guidance on data analysis, reporting recommendations, and consultation of prenatal WGS results.

Uniparental disomy (UPD)-related imprinting disorders are a group of congenital disorders which can lead to severe birth defects. Their molecular etiology is the occurrence of UPD in the genomic imprinting regions, which may cause disturbed expression of parent-of-origin imprinted genes. With the widespread applications of genetic testing techniques, the prenatal diagnosis of UPD-related imprinted diseases has gradually become clinical routines. However, due to the complicated pathogenesis of such disorders, currently there is still a lack of standards and norms for the understanding, diagnosis, management and genetic counseling. By referring to the relevant guidelines and consensus, the latest progress of research, and opinions from experts in the relevant fields, the writing group has formulated a consensus over the prenatal diagnosis and genetic counseling for UPD-related imprinting disorders, with an aim to provide a more accurate and rational evaluation in prenatal clinics.

Objective:To explore the feasibility of non-invasive prenatal testing (NIPT) for detecting fetal chromosomal copy number variants (CNV).Methods:A retrospective analysis was carried out on NIPT positive samples in Suzhou Municipal Hospital from January 1, 2019 to December 31, 2021. The effect of NIPT on fetal CNV detection was assessed by comparison with the results of karyotype analysis and/or chromosomal microarray analysis (CMA).Results:Among the 525 NIPT positive samples, 146 were CNV cases, of which 84 were further verified by karyotyping and/or CMA, 29(34.5%) were true positive. Among them, 12 cases were pathogenic variants, 2 cases were likely pathogenic variants and 15 cases were variants of uncertain significance.Conclusion:NIPT could detect CNV with high accuracy, and to combine CNV detection and chromosomal aneuploidy detection has great significance to improve the prenatal and postnatal care.