OBJECTIVE: To establish a screening model for females of reproductive age carrying Duchenne muscular dystrophy (DMD) variants based on a current community health examination platform. METHODS: A total of 61 870 participants were recruited between October 2017 and October 2019. Serum creatine kinase (CK) was measured with a Roche Cobasc 701/702 using an enzymatic rate method. Genetic testing was offered to those with a CK level of ≥ 200 U/L. For carriers of DMD variants, genetic counseling and follow up were provided. RESULTS: For the 61 870 females participating in the program, 1078 were found with raised serum CK (≥ 200 U/L), of which 618 (57.33%) accepted CK re-measurement after at least a two-week interval. One hundred and twenty cases were found with sustained serum CK elevation, of which 6 were confirmed to be definite DMD carriers regardless of family history. Genetic testing was provided to 33 females with a family history for DMD, and 13 were determined as definite carriers. An affected fetus was detected by prenatal diagnosis. After genetic counseling, the parents had opted induced abortion. CONCLUSION Large-scale DMD carrier screening through a three-step approach based on the current community health examination platform is both feasible and cost effective.
Female ; Genetic Carrier Screening ; Genetic Counseling ; Genetic Testing ; Humans ; Muscular Dystrophy, Duchenne/genetics* ; Pregnancy ; Prenatal Diagnosis

There are a number of novel prenatal cytoogenetic analysis tests for obstetricians and gynecologists on detecting aneuploidies. In the recent years, screening of pregnant patients with non-invasive prenatal testing (NIPT) is one. As the spread of genomic medicine and preventive obstetrics continue, it is prudent for obstetricians and gynecologists to accept and optimize new screening modalities, whenever available. Chromosomal abnormalities are common. Worldwide, one out of 150 live births may involve chromosomal abnormalities. The American College of Obstetrics and Gynecologists (ACOG) and American College of Medical Genetics recommend invasive and non ? invasive prenatal testing (NIPT)3. The invasive testing, however, carries risk for procedure ? related miscarriage. 4This favors NIPT which avoids the risk. The current state of NIPT in the Philippines, is it was only in January 2018, were a NIPT workshop was conducted by the Society of Maternal Fetal Medicine.6 First, due to the minimal studies on personalized and precision medicine on prenatal testing, hence the strong move to conduct this study. In an extensive literature search review in Herdin, a local database and archives of Philippine Obstetrics and Gynecology, none specified researches on non ? invasive prenatal testing. Second, in our country alone, there is no provision for national prenatal tests. In our institution, it was already introduced but with no uptake yet. Because of this gap, scantiness and non - uptake on NIPT locally, hence the conduct of this study. The study aimed to investigate on the obstetricians and gynecologists (OB-GYNs) knowledge, attitude towards and practices (KAP) about NIPT. Majority of the OBGYNs were knowledgeable, had positive attitude and were practicing NIPT. Strikingly, a fourth of the respondents were not comfortable in explaining NIPT. The researcher recommends that there is a need to conduct this study on a larger scale cross - sectional survey and multiple studies due to the paucity of data.
Pregnancy ; Female ; Prenatal Diagnosis ; Genetic Testing ; Mass Screening ; DNA

STUDY DESIGN: Cross-sectional screening. PURPOSE: This study was conducted to determine if there is any association of the three microsatellite markers on chromosome 19p 13.3 in unrelated Saudi Arabian girls who were suffering with adolescent idiopathic scoliosis (AIS) and their healthy siblings. OVERVIEW OF LITERATURE: The genetic influence on the development of familial scoliosis has been previously described, but the genetic influence on AIS still remains unknown. Three microsatellite markers (D19S216, D19S894, and DS1034) of chromosome 19p 13.3 were reported to be significantly associated with familial scoliosis. This cross-sectional screening was carried out in AIS patients and their siblings. METHODS: For eleven Saudi Arabian girls who were treated for AIS and their 11 siblings, we performed a linkage analysis using parametric and nonparametric methods and using GENEHUNTER ver. 2.1. Multipoint linkage analysis was used to specify an autosomal dominant trait with a gene frequency of 0.01 at the genotypic and the allelic levels. One sided Fisher's exact tests were used in the analysis of the contingency tables for the D19S216, D19S894 and DS1034 markers. RESULTS: The analysis between the patient group and the healthy siblings showed that at the genotypic level there was a significant association of the markers and scoliosis (D19S894 [p=0.036], D19S216 [p=0.004], and DS1034 [p=0.013]). Yet at the allelic level, there was no statistically significant association of the markers between the AIS patients and their siblings. CONCLUSIONS: Our pilot study shows that there is a genetic influence between the AIS patients and the siblings. We believe large scale genetic screening is warranted for the patients with AIS to identify beyond any doubt the influence of these markers.
Adolescent ; Arabs ; Genes, vif ; Genetic Markers ; Genetic Testing ; Humans ; Mass Screening ; Microsatellite Repeats ; Pilot Projects ; Scoliosis ; Siblings ; Stress, Psychological

Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that is characterized by an early onset, autosomal dominant mode of inheritance and a primary defect in pancreatic beta-cell function. MODY represents less than 2% of all diabetes cases and is commonly misdiagnosed as type 1 or type 2 diabetes mellitus. At least 13 MODY subtypes with distinct genetic etiologies have been identified to date. A correct genetic diagnosis is important as it often leads to personalized treatment for those with diabetes and enables predictive genetic testing for their asymptomatic relatives. Next-generation sequencing may provide an efficient method for screening mutations in this form of diabetes as well as identifying new MODY genes. In this review, I discuss a current update on MODY in the literatures and cover the studies that have been performed in Korea.
Diabetes Mellitus, Type 2* ; Diagnosis ; Genetic Testing ; Humans ; Korea ; Mass Screening ; Wills

China ; Genetic Testing ; Hearing ; Hearing Tests ; Humans ; Infant, Newborn ; Neonatal Screening

OBJECTIVE: To analyze the clinical and genetic features of two children suspected for arginylsuccinuria aciduria. METHODS: The patients were subjected to high-throughput sequencing using a gene panel. RESULTS: Both patients had high citrulline (87.37-156.10 μmol/L) measured by mass spectrometry/mass spectrometry (MS/MS) upon neonatal screening but had no symptoms. Two compound heterozygous variants of the ASL gene were detected in patient 1 (exon 6: c.467C>T inherited from her father and exon 7: c.556C>T inherited from her mother), among which c.556C>T is novel. Patient 2 had mental retardation and two full siblings who had died of hyperammonemia. Two compound heterozygosity variants of the ASL gene were detected (exon 3: c.281G>T inherited from his father and intron: c.208-15T>A inherited from his mother). Both were novel mutations. CONCLUSION Variants of the ASL gene probably underlie the argininosuccinic aciduria in the two patients. Above findings have enriched the spectrum of ASL mutations.
Argininosuccinic Aciduria ; Child ; Female ; Genetic Testing ; Humans ; Hyperammonemia ; Infant, Newborn ; Neonatal Screening ; Tandem Mass Spectrometry

OBJECTIVE: To explore the clinical and genetic characteristics of four patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD). METHODS: Four children who had presented at the Children's Hospital Affiliated to Zhengzhou University between August 2019 and August 2021 were selected as the study subjects. Clinical data of the children were collected. The children were subjected to whole exome sequencing (WES). RESULTS: All of the four children were diagnosed with MCADD. Blood amino acid and ester acyl carnitine spectrum test showed that the concentration of octanoyl carnitine (C8) was significantly increased. The main clinical manifestations included poor mental response (3 cases), intermittent diarrhea with abdominal pain (1 case), vomiting (1 case), increased transaminase (3 cases), and metabolic acidosis (2 cases). Five variants were identified by genetic testing, among which c.341A>G (p.Y114C) was unreported previously. Three were missense variants, one was frameshift variant and one was splicing variant. CONCLUSION The clinical heterogeneity of MCADD is obvious, and the severity of the disease may vary. WES can assist with the diagnosis. Delineation of the clinical symptoms and genetic characteristics of the disease can facilitate early diagnosis and treatment of the disease.
Child ; Humans ; Acyl-CoA Dehydrogenase/genetics* ; Carnitine ; Genetic Testing ; Lipid Metabolism, Inborn Errors/genetics* ; Neonatal Screening

Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and regulations and the leadership of the national health administration, approved screening centers in public hospitals took the responsibility for publicity, screening, diagnosis, treatment, follow-up and management of birth defects. As of 2022, 31 provinces (autonomous regions and municipalities directly under the central government) have carried out NBS for phenylketonuria, congenital hypothyroidism, and hearing loss, 23 provinces have carried out screening for glucose-6-phosphate dehydrogenase (with a screening rate of 89.24%), and 24 provinces have carried out screening for congenital adrenal cortical hyperplasia (91.45% screening rate). Over the past four decades, screening techniques have evolved from bacterial inhibition, fluorescence analysis, and tandem mass spectrometry for the detection of biochemical markers to genetic testing, which has greatly contributed to the expansion of the types of diseases screened for. The combined use of metabolomics and genomics is currently being explored. Effective management and rigorous quality control of NBS are prerequisites for improving the quality and ensuring the accuracy of screening. The Quality Management System for Newborn Screening System Network (QMS-NBS), established by the National Center for Clinical Laboratories, covers all screening centers and related blood collection agencies. The operation of the QMS-NBS allows the quality and performance of screening to be transparent and measurable, ensuring the quality and efficiency of screening. This article provides an overview of the history of NBS, especially the evolution of policies for the NBS in China, the construction of screening institutions, the number of newborns screened, the incidence rates of screened diseases, the changes in screening technology, the expansion of new diseases screened for, and the quality control of NBS. Overall, the progress in NBS in China has not only benefited from the development and standardization at the technological level, but also benefited from the construction of policies, regulations and ethics.
Infant, Newborn ; Humans ; Neonatal Screening ; Phenylketonurias ; Genetic Testing ; Congenital Hypothyroidism ; China

Completion of the human genome project has allowed a deeper understanding of molecular pathophysiology and has provided invaluable genomic information for the diagnosis of genetic disorders. Advent of new technologies has lead to an explosion in genetic testing. However, this overwhelming stream of genetic information often misleads physicians and patients into a misguided faith in the power of genetic testing. Moreover, genetic testing raises a number of ethical, legal, and social issues. Diagnostic genetic tests can be divided into three primary but overlapping categories: cytogenetic studies (including routine karyotyping, high-resolution karyotyping, and fluorescent in situ hybridization studies), biochemical tests, and DNA-based diagnostic tests. DNA-based testing has grown rapidly over the past decade and includes preand postnatal testing for the diagnosis of genetic diseases, testing for carriers of genetic diseases, genetic testing for susceptibility to common non-genetic diseases, and screening for common genetic diseases in a particular population. Theoretically, once a gene's structure, function, and association with a disease are well established, the clinical application of genetic testing should be feasible. However, for routine applications in a clinical setting, such tests must satisfy a number of criteria. These criteria include an acceptable degree of clinical and analytical validity, support of a quality assurance program, possibility of modifying the course of the diagnosed disease with treatment, inclusion of pre-and postnatal genetic counseling, and determination of whether the proposed test satisfies cost-benefit criteria and should replace or complement traditional tests. In the near future, the application of genetic testing to common diseases is expected to expand and will likely be extended to include individual pharmacogenetic assessments.
Complement System Proteins ; Cytogenetics ; Diagnostic Tests, Routine ; Explosions ; Genetic Counseling ; Genetic Testing ; Human Genome Project ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Mass Screening ; Rivers

OBJECTIVETo identify the molecular etiopathogenesis for a non-syndromic hearing loss patient.

METHODSThe core family, consists of the patient and his parents, was recruited. Genomic DNA was extracted from peripheral blood. Mutation analysis was carried out by SNaPshot and next-generation sequencing technology. Mutations in SLC26A4 gene were verified by polymerase chain reaction and direct sequencing.

RESULTSCompound heterozygous mutations p.V306GfsX24 and p.P516PfsX11 in SLC26A4 gene were detected in the patient, heterozygous mutation p.V306GfsX24 was detected in the father, heterozygous mutation p.P516PfsX11 was detected in the mother.

CONCLUSIONSCompound heterozygous mutations p.V306GfsX24 and p.P516PfsX11 contributed to patient's hearing loss. Next-generation sequencing technology is a useful tool for detecting de novo mutations of deafness genes, and is suitable for clinical application.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Child ; DNA Mutational Analysis ; Deafness ; genetics ; Female ; Genetic Carrier Screening ; Genetic Testing ; Humans ; Male ; Membrane Transport Proteins ; genetics ; Mutation ; Pedigree