OBJECTIVE: To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition. METHODS: Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed. RESULTS: Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects. CONCLUSION Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.
Humans ; Female ; Pregnancy ; Ultrasonography, Prenatal ; DiGeorge Syndrome/genetics* ; Adult ; Male ; Follow-Up Studies ; Fetus/diagnostic imaging* ; Phenotype ; Infant, Newborn

OBJECTIVE: To analyze the phenotype and genotype of a neonate with Osteo-oto-hepato-enteric syndrome (O2HE) and review the literature. METHODS: A female neonate diagnosed with O2HE syndrome on December 13, 2024 at the First Affiliated Hospital of Zhengzhou University was selected as the study subject, and her clinical characteristics were analyzed, and pathogenic variants were explored by whole exome sequencing (WES). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-KY-1038). RESULTS: The proband, a female infant, was delivered by Cesarean section at 36⁺¹ weeks of gestation. Five days after birth, she had developed severe diarrhea, mild cholestasis, sensorineural hearing loss, and growth retardation. WES revealed that she has harbored novel compound heterozygous variants c.512delA (p.Lys171Serfs*64) and c.698C>A (p.Thr233Asn) of the UNC45A gene, which were inherited from her mother and father, respectively. A total of 8 English papers were retrieved, which involved 16 patients from 14 families. Combined with our case, the 17 patients included 13 (76.5%) females and 4 (23.5%) males. Four patients (23.5%) had consanguineous parents. One case was excluded from further genetic analysis due to co-morbidity with other genetic variants. The primary clinical features included diarrhea (87.5%), cholestasis (81.3%), sensorineural hearing loss (31.3%), bone fragility (37.5%), and developmental delay (50.0%). Bi-allelic compound heterozygous mutations were identified in 12 patients (75.0%), and homozygous variants in 4 (25.0%). These included missense, nonsense, frameshift and deletional variants. The c.710T>C (p.Leu237Pro) variant was identified for 5 times, 3 of which were in homozygote forms. CONCLUSION O2HE syndrome should be suspected in cases with diarrhea, cholestasis, and hearing abnormalities during early postnatal period. Genetic testing facilitate early identification, genetic diagnosis and treatment.
Humans ; Female ; Infant, Newborn ; Male ; Mutation ; Hearing Loss, Sensorineural/genetics* ; Diarrhea, Infantile/genetics* ; Exome Sequencing ; Phenotype ; Fetal Growth Retardation ; Hair Diseases ; Facies

OBJECTIVE: To explore the serological and molecular genetic characteristics of a family with subtype B(A)06. METHODS: A neonatal hyperbilirubinemia patient who was treated at Henan Children's Hospital on June 15, 2023 due to "yellowing of the skin and gradual aggravation", and was found to have inconsistent ABO forward and reverse typing through blood type testing, was selected as the research subject. Six milliliters of peripheral blood were collected from the newborn and her family members (grandfather, grandmother, father, mother and aunt) respectively. ABO blood group identification was performed by the blood group serological method. Human genomic DNA was extracted using the nucleic acid extraction or purification reagent BT-01. ABO gene exons 2 to 7 were amplified by PCR. The PCR-specific products that were successfully amplified were sequenced by Sanger method. Taking ABO*A1.01 as the reference sequence, the ABO gene sequences of the newborn and her family members were analyzed to determine the ABO genotype. The procedures followed in this study were approved by the Ethics Committee of Henan Children's Hospital (Ethics No.: 2022-K-L036). RESULTS: The serological results of ABO blood group showed that the newborn, her grandfather, father and aunt were all incompatible with the forward and reverse typing. The blood group phenotype of the newborn was AwB or B(A), the blood group phenotype of the grandfather was A2B or B(A), the blood group phenotype of the father and aunt were A2B, and the blood group phenotype of the grandmother and mother were both O. The screening test results of hemolytic disease of the newborn showed that the free test detected IgG anti-A1 antibody, while the elution test, direct antiglobulin test and antibody screening results were all negative. The Sanger sequencing results showed that the newborn had variations of c.261delG, c.297A>G, c.526C>G, c.657C>T, c.703G>A, c.796C>A and c.930G>A. Her grandfather had variations of c.297A>G, C.526C>G, c.657C>T, c.703G>A, c.796C>A, c.803G>C and c.930G>A. Her grandmother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T and c.829G>A. Her father and aunt had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.526C>G, c.646T>A, c.657C>T, c.681G>A, c.703G>A, c.771C>T, c.796C>A, c.829G>A and c.930G>A. Her mother had variations of c.106G>T, c.188G>A, c.189C>T, c.220C>T, c.261delG, c.297A>G, c.646T>A, c.681G>A, c.771C>T, and c.829G>A.The genotype of the newborn was ABO*BA.06/ABO*O.01.01, her grandfather was ABO*BA.06/ABO*B.01, her grandmother was ABO*O.01.02/ABO*O.01.02, her father and aunt were ABO*BA.06/ABO*O.01.02, and her mother was ABO*O.01.01/ABO*O.01.02. The ABO*BA.06 allele of the newborn, grandfather, father and aunt was caused by the c.803C>G variation in exon 7 based on the ABO*B.01 allele. The ABO*BA.06 allele can be stably inherited in this family. CONCLUSION The blood type of neonatal patients with B(A)06 subtype can be accurately determined by gene sequencing technology. If the forward typing is ≤ 3+ agglutination intensity in newborn ABO blood group identification, the reason should be carefully analyzed, and the molecular biology technology and family gene sequencing results should be used to jointly determine if necessary.
Humans ; ABO Blood-Group System/genetics* ; Female ; Pedigree ; Male ; Infant, Newborn ; Asian People/genetics* ; Genotype ; China ; Blood Grouping and Crossmatching ; Hyperbilirubinemia, Neonatal/blood* ; East Asian People

OBJECTIVE: To elucidate the epidemiological characteristics and genetic variant profile of Short-chain acyl-CoA dehydrogenase deficiency (SCADD) among newborns from Hainan Province and evaluate its significance within the local neonatal disease screening panel. METHODS: A total of 84 184 newborns born in Hainan Province from February to December 2024 were included. Tandem mass spectrometry (MS/MS) was employed to detect butyrylcarnitine (C4) and propionylcarnitine (C3) levels in dried blood spots. Screening thresholds were set at C4 > 0.43 μ mol/L and C4/C3 ratio > 0.28. Suspected cases underwent confirmatory testing via urinary ethylmalonic acid analysis by gas chromatography-mass spectrometry and whole-exome sequencing for ACADS gene variants. This study was approved by the Medial Ethics Committee of the hospital (Ethics No.: HNWCMC-2024-55). RESULTS: Six SCADD cases (male-to-female ratio = 1:1) were diagnosed, with all carrying compound heterozygous variants at two loci, yielding a prevalence of 7.13 per 100,000 live births. Four known ACADS gene variants were identified, with both c.322G>A and c.625G>A detected at a frequency of 41.7%. Regular follow-up (as of January 2026) revealed that all diagnosed cases have remained asymptomatic with normal growth and development. CONCLUSION The prevalence of SCADD among newborns in Hainan Province is relatively high, with c.322G>A and c.625G>A as the hotspot variants in the region. Given the absence of clinical phenotypes in all screen-detected cases during long-term follow-up, it is recommended to remove this condition from the routine neonatal screening program for this region to reduce unnecessary anxiety and medical cost.
Humans ; Infant, Newborn ; Neonatal Screening/methods* ; Female ; Male ; Lipid Metabolism, Inborn Errors/epidemiology* ; Acyl-CoA Dehydrogenase/genetics* ; China/epidemiology* ; Follow-Up Studies

BACKGROUND

Child malnutrition is a prevailing global public health concern especially in low- and middle-income countries. Conditional cash transfer (CCT) programs were implemented to help address this problem.

To determine the relationship between the nutritional status among 0-59 months old children and household enrollment in a Philippine CCT program, Pantawid Pamilyang Pilipino Program (4Ps).

A cross-sectional study was employed to 392 children and mothers/primary caregivers in a rural municipality in Leyte. Stratified random sampling technique was used in selecting the participants. Anthropometric characteristics were measured for these 392 children and were classified as 4Ps and non-4Ps members. Chi-square test was used to determine the relationship between the variables of interest.

4Ps household beneficiaries had mothers/primary caregivers who were older and had fewer years of education. The 4Ps beneficiary households had more household members and had lower average monthly income compared to the non-beneficiaries. No significant differences were found between the 4Ps beneficiary and non-beneficiary households in terms of the household hunger scale, the mean age of the children, and the sex distribution of the children included in the study. Specific profile components were found to be correlated to the children’s nutritional status. The age of the children was significantly associated to their length/height-for-age (L/HFA) wherein stunting was noted to occur among children older than 12 months of age. Maternal education was significantly associated to the weight-for-age (WFA) of the children. Children who were underweight had mothers/primary caregivers with fewer years of education. No significant correlation was found between the child’s sex, age of the mother/primary caregiver, household size, average monthly household income, and household hunger scale and the children’s nutritional status Lastly, there was no significant correlation between 4Ps household enrollment and the WFA and L/HFA status of the children. 4Ps household enrollment was, however, significantly correlated to the weight-for-length/height (WFL/H) or wasting status of the children.

The 4Ps program has the potential to enhance the nutritional outcomes of children hence the need to maximize its gains. In addition, the relationship of different sociodemographic variables with the children’s nutritional status reflects the complexity and multidimensionality of childhood malnutrition, implying the need for a holistic and multistakeholder approach in addressing the problem.

OBJECTIVE: To explore the results of four types of Urea cycle disorders (UCDs) in newborns from the Xuzhou region, assess the efficacy of newborn screening by tandem mass spectrometry (MS/MS), and analyze their genetic characteristics. METHODS: A retrospective analysis was performed using tandem mass spectrometry to screen for inherited metabolic disorders in 691 712 newborns at the Maternal and Child Health Care Hospital of Xuzhou from November 2015 to December 2023. Ten children (cases 1-10) were diagnosed with Ornithine transcarbamylase deficiency (OTCD), Carbamoylphosphate synthase 1 deficiency (CPS1D), Arginase deficiency (ARGD), and Argininosuccinate synthase deficiency (ASSD) based on MS/MS and genetic testing. This study was approved by the Medical Ethics Committee of Xuzhou Maternity and Child Health Care Hospital (Ethics No.XZFY2024-051K-01J). RESULTS: A total of 691 712 neonates were screened for UCDs using MS/MS, which identified 1 237, 1 237, 510, and 1 009 initial positive cases for OTCD, CPS1D, ASSD, and ARGD, respectively. After genetic testing, 1 case of OTCD, 1 case of CPS1D, 1 case of ASSD, and 7 cases of ARGD were confirmed. The overall positive predictive value for these four UCDs was 0.362%. Among the 10 diagnosed UCD cases, four novel variants were identified, which included OTC: c.1024C>A (p.L342M) and ASS1: c.826A>G (p.M276V), c.695C>T (p.P232L) and c.694C>T (p.P232S). Bioinformatic analysis has rated these as variants of uncertain clinical significance or likely pathogenic based on guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The incidence of four UCDs in neonates from the Xuzhou area is relatively low, and there is a correlation between genetic variants and clinical phenotypes. For novel variants with uncertain clinical significance or suspected pathogenicity, their pathogenicity should be clarified in conjunction with clinical and biochemical indicators. The four novel pathogenic variants of UCDs identified in this study have enriched the mutational spectrum of UCDs-associated genes in the Xuzhou region.
Humans ; Infant, Newborn ; Tandem Mass Spectrometry/methods* ; Urea Cycle Disorders, Inborn/diagnosis* ; Neonatal Screening/methods* ; Genetic Testing/methods* ; Female ; Retrospective Studies ; Male ; Ornithine Carbamoyltransferase Deficiency Disease/diagnosis* ; Mutation ; Carbamoyl-Phosphate Synthase (Ammonia)/genetics* ; Ornithine Carbamoyltransferase/genetics*

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a neonate with X-linked alpha-thalassemia mental retardation syndrome (ATR-X) caused by ATRX gene variant, and review related literature on children with ATR-X caused by ATRX gene variants. METHODS: A case of ATR-X neonate who was transferred to the First Affiliated Hospital of Zhengzhou University on February 11, 2022 for poor effect of treatment in the neonatology department of the hospital where he was born for 4 days due to "postnatal slow response, groaning, and cyanosis of the skin for 30 min" was selected as the study subject. 3 mL of peripheral blood was collected from the child and their parents, and genomic DNA was extracted for whole exome sequencing (WES). Sanger sequencing was used to verify the pathogenic gene variations in the child's family. The pathogenicity of genetic variant sites was assessed based on the Standards and Guidelines for the Interpretation of Sequence Variants by American College of Medical Genetics and Genomics (ACMG). The amino acid sequence conservation analysis of relevant variant proteins was conducted by the Universal Protein Resource Database (UniProt) and visual analysis of these variant proteins was performed by Swiss online protein three-dimensional modeling database (SWISS-MODEL). Using keywords such as "ATRX gene" and " X-linked alpha-thalassemia mental retardation syndrome" both in Chinese and English, relevant literature on ATR-X children caused by ATRX gene variants was retrieved from the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases, and the clinical phenotypes of ATR-X patients reported in the retrieved literature were analyzed. The literature retrieval time was set from the establishment of each database to December 31st, 2023. This study followed the research procedures approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University (Ethics No. 2023-KY-1360-002), and informed consent of clinical study was signed by the guardian of the child. RESULTS: The child in this study presented with symptoms such as delayed response, feeding difficulties accompanied by vomiting, low body temperature, hypotonia in all extremities, apnea, abnormal hearing screening, and a Neonatal Behavioral Neurological Assessment (NBNA) score of 19 (lower than the normal range).Hemoglobin (Hb) electrophoresis suggested the presence of α-thalassemia. The results of WES and Sanger sequencing revealed a hemizygous missense variant c.668G>A (p.C223Y) in exon 9 of the ATRX gene in the child of the study, neither of the parents of the child carried this variant, indicating that it is a de novo variant. Based on the Standards and Guidelines for the Interpretation of Sequence Variants released by ACMG, this gene variant was assessed as pathogenic (PS2+PM2_Supporting+PP3_Strong+PP4_Strong). The results of amino acid sequence analysis revealed that the pathogenic variant site normally encodes cysteine, which is highly conserved among various animal species. This pathogenic variant can lead to alterations in the hydrogen bonding structure of ATRX protein, thereby affecting its structural stability. Based on the clinical manifestations and genetic testing results of the child in this study, a diagnosis of ATR-X syndrome was established Based on the literature retrieval strategy established in this study, 13 relevant articles concerning ATR-X syndrome in children caused by ATRX gene variants were retrieved, including 5 Chinese articles and 8 English articles, involving a total of 311 ATR-X children. Including the child in this study, the total number of ATR-X children reaches 312. All 312 children were male and presented with mental retardation. Among them, 45.8% (143/312) had coexisting α-thalassemia, 45.2% (141/312) had abnormal genital appearance, 44.2% (138/312) had facial malformations, and 30.8% (96/312) had hypotonia. Other phenotypes included microcephaly, skeletal dysplasia, among others. CONCLUSION The ATR-X child in this study exhibit a range of clinical phenotypes, including delayed growth and development, facial malformation, abnormal genital appearance, apnea, vomiting symptoms, among others. The de novo variant of ATRX gene c.668G>A (p.C223Y) was identified as the genetic etiology. This study contributes to the expansion of the clinical phenotype spectrum and genetic variation spectrum of ATR-X children.
Humans ; X-linked Nuclear Protein/genetics* ; alpha-Thalassemia/genetics* ; X-Linked Intellectual Disability/genetics* ; Male ; Infant, Newborn ; Exome Sequencing ; Mutation

OBJECTIVE: To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS). METHODS: A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children's Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01). RESULTS: The infant was born prematurely at 35⁺³ weeks due to "premature rupture of membranes for 4 hours" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c.1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father. CONCLUSION This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c.1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.
Humans ; Serine Peptidase Inhibitor Kazal-Type 5/genetics* ; Netherton Syndrome/genetics* ; Female ; Infant, Newborn ; Infant, Premature ; Mutation ; Exome Sequencing ; Male

OBJECTIVE: To provide preimplantation genetic testing (PGT) for a patient with Incontinentia pigmenti (IP) due to IKBKG gene variant but without family samples through construction of single nucleotide polymorphism (SNP)-based haplotype by Long-read sequencing (LRS) technology. METHODS: A female IP patient with a heterozygous IKBKG c.1167dup variant but without family genetic data who sought genetic counseling at Women and Children' Hospital of Ningbo University in November 2021 was selected as the study subject. The IKBKG gene has a highly homologous pseudogene IKBKGP1. Genomic DNA was extracted from peripheral blood samples from the couple, and LRS was used to obtain informative SNP loci flanking the variant locus, enabling the construction of SNP haplotype with a long segment spanning from the non-homologous region of IKBKG to the variant site. Trophoblast cells were biopsied from blastocysts fertilized through intracytoplasmic sperm injection, and next-generation sequencing (NGS) was used to determine the SNP information of the embryos. Linkage analysis with the parental SNP haplotypes was conducted to detect the carrier status of the embryos and exclude chromosomal aneuploidies. Sanger sequencing was carried out to validate the result. A euploid embryo without the pathogenic variant was selected for transfer. Prenatal diagnosis was carried out by amniocentesis at mid-trimester to verify the result of PGT tests, and follow-up was conducted after the baby was born. This study has been approved by the Ethics Committee of Women and Children's Hospital of Ningbo University (Ethics No. EC2023-094). RESULTS: A total of seven blastocysts were tested, and PGT results indicated that two embryos were euploid and did not carry the pathogenic variant. One euploid embryo was transferred, which resulted in a singleton pregnancy. Amniocentesis at 24 weeks of gestation confirmed that the status of fetal IKBKG gene, and its chromosomal status was consistent with the PGT results. A healthy male infant was born at 38+6 weeks of gestation. CONCLUSION For IP patients with de novo mutation or without family genetic samples, PGT with LRS can directly construct the SNP-based haplotype while avoiding interference from pseudogenes, providing an effective strategy for PGT.
Female ; Humans ; Male ; Pregnancy ; Genetic Testing/methods* ; Haplotypes/genetics* ; High-Throughput Nucleotide Sequencing/methods* ; I-kappa B Kinase/genetics* ; Incontinentia Pigmenti/diagnosis* ; Polymorphism, Single Nucleotide/genetics* ; Preimplantation Diagnosis/methods* ; Infant, Newborn