Improving methylmalonic acidemia (MMA) screening and MMA genotype prediction using random forest classifier in two Chinese populations.

Background: Methylmalonic acidemia (MMA) is one of the most common hereditary organic acid metabolism disorders that endangers the lives and health of infants and children. Early detection and intervention before the appearance of a newborn's clinical symptoms can control disease progression and prevent or mitigate its serious consequences.

Methods: 42,004 newborns from two Chinese populations were included in the study.

Mutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants.

Background: Hearing loss (HL) is the most frequent sensory deficit in humans, with strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counselling for the patient's family.

Methods: We detected and analysed 362 Chinese non-syndromic HL patients by screening of variants in 15 hot spot mutations.

[Clinical and molecular genetic analysis of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome].

Objective: To explore the genetic characteristics of a child with comorbid 16p11.2 microdeletion syndrome and Rett syndrome (RTT).

Methods: A male infant who was admitted to Gansu Provincial Maternity and Child Health Care Hospital in May 2020 was selected as the study subject.

Analysis of spinal muscular atrophy carrier screening results in 32,416 pregnant women and 7,231 prepregnant women.

Objectives: Spinal muscular atrophy (SMA) is an autosomal recessive disease that is one of the most common in childhood neuromuscular disorders. Our screenings are more meaningful programs in preventing birth defects, providing a significant resource for healthcare professionals, genetic counselors, and policymakers involved in designing strategies to prevent and manage SMA.

Method: We screened 39,647 participants from 2020 to the present by quantitative real-time PCR, including 7,231 pre-pregnancy participants and 32,416 pregnancy participants, to detect the presence of SMN1 gene EX7 and EX8 deletion in the DNA samples provided by the subjects.

Result of a Pilot External Quality Assessment Scheme for Clinical Diagnosis of Inherited Metabolic Disorders in China.

Background: We aimed to evaluate the diagnostic capabilities of Chinese laboratories for inherited metabolic disorders (IMDs) using gas chromatography-mass spectrometry (GC-MS) on urine samples. Meanwhile, based on the result of the pilot external quality assessment (EQA) scheme, we hope to establish a standardized and reliable procedure for future EQA practice.

Methods: We recruited laboratories that participated in the EQA of quantitative analysis of urinary organic acids with GC-MS before joining the surveys.

[Clinical and genetic analysis of two pedigrees affected with Carnitine-acylcarnitine translocase deficiency due to variant of SLC25A20 gene].

Objective: To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency (CACTD).

Methods: Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis.

[Analysis of a patient with Retinitis pigmentosa due to a novel variant of IMPDH1 gene].

Objective: To explore the genetic basis for a patient with autosomal dominant retinitis pigmentosa (RP).

Methods: A male patient with RP treated at Gansu Provincial Maternal and Child Health Care Hospital in September 2019 was selected as the study subject. Clinical data was collected.

Combined Amniotic Membrane and Self-Powered Electrical Stimulator Bioelectronic Dress Promotes Wound Healing.

Human amniotic membranes (hAMs) are widely used as wound management biomaterials, especially as grafts for corneal reconstruction due to the structure of the extracellular matrix and excellent biological properties. However, their fragile nature and rapid degradation rate hinder widespread clinical use. In this work, we engineered a novel self-powered electronic dress (E-dress), combining the beneficial properties of an amniotic membrane and a flexible electrical electrode to enhance wound healing.

[Genetic analysis and prenatal diagnosis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency and MECP2 duplication syndrome].

Objective: To explore the genetic basis for a Chinese pedigree affected with co-morbid Ornithine carbamoyl transferase deficiency (OTCD) and MECP2 duplication syndrome.

Methods: A proband who was admitted to the Neonatal Intensive Care Unit of Gansu Provincial Maternal and Child Health Care Hospital on December 19, 2017 was selected as the study subject. High-throughput sequencing and multiplex ligation-dependent probe amplification (MLPA) were carried out for her pedigree, and short tandem repeat-based linkage analysis and chromosome copy number variation sequencing (CNV-seq) were used for the prenatal diagnosis.

[Genetic analysis of eighteen patients from Gansu Province with Tetrahydrobiopterin deficiency].

Objective: To explore the genetic basis of eighteen patients with Tetrahydrobiopterin deficiency (BH4D) from Gansu Province.

Methods: Eighteen patients diagnosed with BH4D at Gansu Provincial Maternal and Child Health Care Hospital from January 2018 to December 2021 were selected as the study subjects. Whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing.

Novel de novo mutation in ZBTB20 in a Chinese Primrose syndrome family and a review of the literature.

Background: Primrose syndrome is an autosomal dominant disorder characterized by craniofacial dysmorphism, mental retardation, developmental delay, progressive muscle atrophy and calcification of the earlobe due to a mutation in the ZBTB20.

Method: We reported a case of a Chinese boy with clinical symptoms resembling Primrose Syndrome, and performed genetic etiology analysis of the proband's family through Trio whole exome sequencing.

Result: A novel missense variant c.

Immune skeletal dysplasia with neurodevelopmental abnormalities caused by a novel variant of EXTL3 gene in a Chinese family.

Background: Immune skeletal dysplasia with neurodevelopmental abnormalities (ISDNA) is an extremely rare, autosomal recessive genetic disorder characterized by various skeletal abnormalities, neurodevelopmental deficits, and abnormal immune system function. ISDNA is caused by variation in the exostosin-like 3 (EXTL3) gene, located on chromosome 8p21.2, whose primary function is the biosynthesis of heparan sulfate (HS) skeleton structure.

Accuracy and depth evaluation of clinical low pass genome sequencing in the detection of mosaic aneuploidies and CNVs.

Background: Low-pass genome sequencing (LP GS) has shown distinct advantages over traditional methods for the detection of mosaicism. However, no study has systematically evaluated the accuracy of LP GS in the detection of mosaic aneuploidies and copy number variants (CNVs) in prenatal diagnosis. Moreover, the influence of sequencing depth on mosaicism detection of LP GS has not been fully evaluated.

[Clinical features and genetic analysis of a child with 3-methylglutenedioic aciduria type VII due to novel variants of CLPB gene].

Objective: To explore the clinical features and genetic basis for a child with 3-methylglutaconic aciduria type VII.

Methods: A child who was diagnosed at the Gansu Provincial Maternity and Child Health Care Hospital on August 9, 2019 was selected as the study subject. Clinical data of the child, including urine gas chromatography and mass spectrometry, were collected.

Evaluation of the clinical effects of non-invasive prenatal screening for diseases associated with aneuploidy and copy number variation.

Background: To explore and compare the clinical effects of high-resolution non-invasive prenatal screening (NIPS-Plus) for common/uncommon chromosomal aneuploidy and microdeletion/microduplication syndromes (MMS).

Methods: The current prospective study included a total of 25,380 pregnant women who performed NIPS-Plus, and amniocentesis was performed on women with MMS with the screening results to diagnose patients with suspected MMS.

Results: There were 415 samples with positive results for NIPS-Plus, included 275 with aneuploidy and 140 with MMS.

Identification of deep intronic variants of PAH in phenylketonuria using full-length gene sequencing.

Background: Phenylketonuria (PKU) is an autosomal recessive congenital metabolic disorder caused by PAH variants. Previously, approximately 5% of PKU patients remained undiagnosed after Sanger sequencing and multiplex ligation-dependent probe amplification. To date, increasing numbers of pathogenic deep intronic variants have been reported in more than 100 disease-associated genes.

[Genetic analysis of a child with Pitt-Hopkins syndrome due to a novel variant of TCF4 gene derived from low percentage maternal mosaicism].

Objective: To explore the genetic etiology of a child with Pitt-Hopkins syndrome.

Methods: A child who had presented at the Medical Genetics Center of Gansu Provincial Maternal and Child Health Care Hospital on February 24, 2021 and his parents were selected as the study subjects. Clinical data of the child was collected.

[Prenatal diagnosis for a fetus with Walker-Warburg syndrome].

Objective: To explore the genetic etiology for a fetus with Walker-Warburg syndrome(WWS).

Methods: A fetus with WWS diagnosed at Gansu Provincial Maternity and Child Health Care Hospital in June 9, 2021 was selected as the study subject. Genomic DNA was extracted from amniotic fluid sample of the fetus and peripheral blood samples from its parents.

The spectrum of phenylalanine hydroxylase variants and genotype-phenotype correlation in phenylketonuria patients in Gansu, China.

Background: Phenylketonuria (PKU) is a common, congenital, autosomal recessive, metabolic disorder caused by Phenylalanine hydroxylase (PAH) variants.

Methods: 967 PKU patients from Gansu, China were genotyped by Sanger sequencing, multiplex ligation-dependent probe amplification, and whole exome sequencing. We analyzed the variants of PAH exons, their flanking sequences, and introns.

[Clinical features and genetic analysis of a child with acute form of Tyrosinemia type I due to a novel variant of FAH gene].

Objective: To analyze the clinical phenotype and genetic basis for a child with acute form of tyrosinemia type I (TYRSN1).

Methods: A child with TYRSN1 who presented at the Gansu Provincial Maternal and Child Health Care Hospital in October 2020 was selected as the subject. The child was subjected to tandem mass spectrometry (MS-MS) and urine gas chromatography-mass spectrometry (GC-MS) for the detection of inherited metabolic disorders, in addition with whole exome sequencing (WES).

[Analysis of genotypes and phenotypes of three children with Cornelia de Lange syndrome].

Objective: To analyze the clinical phenotype and results of genetic testing in three children with Cornelia de Lange syndrome (CdLS).

Methods: Clinical data of the children and their parents were collected. Peripheral blood samples of the pedigrees were collected for next generation sequencing analysis.

Random forest classifier improving phenylketonuria screening performance in two Chinese populations.

Phenylketonuria (PKU) is a genetic disorder with amino acid metabolic defect, which does great harms to the development of newborns and children. Early diagnosis and treatment can effectively prevent the disease progression. Here we developed a PKU screening model using random forest classifier (RFC) to improve PKU screening performance with excellent sensitivity, false positive rate (FPR) and positive predictive value (PPV) in all the validation dataset and two testing Chinese populations.