OBJECTIVE: To analyze the association between pulmonary surfactant protein C (SP-C) gene polymorphisms and the risk of Neonatal respiratory distress syndrome (NRDS). METHODS: Clinical data from 168 neonates diagnosed with NRDS (NRDS group) admitted between August 2020 and June 2023 were collected. Additionally, 168 neonates without respiratory distress, born during the same period, were included as the control group. Peripheral venous blood samples (2 mL each) were collected from both groups. PCR-restriction fragment length polymorphism technique was employed to detect the polymorphisms at the SP-C gene loci p.Thr138Asn (rs4715) and p.Ser186Asn (rs1124). Hardy-Weinberg equilibrium tests were conducted for genotyping, and genotypic and allelic frequencies were compared. The association between SP-C gene polymorphisms and NRDS risk was evaluated. Furthermore, genotypic and allelic frequencies at the rs4715 and rs1124 loci were compared among NRDS cases with varying degrees of disease severity. The study was approved by the Medical Ethics Committee of Shangqiu First People's Hospital (Ethics No. 2020-031). RESULTS: The frequency of the variant allele (A) at the rs4715 locus was significantly higher in the NRDS group compared to the control group (32.14% vs. 24.11%, P = 0.001). The frequency of the variant genotype (AA + AC) was also higher in the NRDS group (47.02% vs. 39.29%, P = 0.043). The frequency of the variant allele (A) at the rs1124 locus was higher in the NRDS group compared to the control group (34.23% vs. 23.51%, P = 0.027), with a higher frequency of the variant genotype (AA + AG) in the NRDS group (49.40% vs. 39.29%, P = 0.019). No significant correlation was observed between the rs4715 polymorphism and the severity of NRDS (P > 0.05). Among NRDS children with grade III severity, the frequency of the variant allele (A) at the rs1124 locus was higher than in grade I and grade II children (47.62% vs. 29.22%, P = 0.020). The frequency of the variant genotype (AA + AG) was also higher in grade III children (64.28% vs. 43.84%, P = 0.040). CONCLUSION SP-C gene polymorphisms are associated with the susceptibility to NRDS. Neonates carrying the AA genotype and the A allele at the rs1124 locus are at a higher risk of severe NRDS. These findings have provided further evidence for early screening, diagnosis, and treatment of NRDS.
Humans ; Respiratory Distress Syndrome, Newborn/genetics* ; Infant, Newborn ; Gene Frequency ; Genotype ; Polymorphism, Single Nucleotide ; Pulmonary Surfactant-Associated Protein C/genetics* ; Genetic Predisposition to Disease ; Female ; Male ; Alleles

Brain-lung-thyroid syndrome is a rare autosomal dominant disorder. More than 100 cases have been reported worldwide, but few cases have been reported in China. In December 2018, a boy with brain-lung-thyroid syndrome, aged 3 years and 10 months, was admitted to Xiangya Hospital of Central South University due to repeated cough for more than 3 years. In infancy of the boy, psychomotor retardation, repeated cough, and hypothyroidism were found. Gene detection showed that there was c.927delc heterozygous variation in NKX2-1 gene (NM-001079668: exon3: c.927delC). The variation of this gene locus has not been reported in relevant literature so far, which indicates a new mutation. According to the above clinical manifestations and examination results, the boy was diagnosed as brain-lung-thyroid syndrome, which mainly characterized by nervous system disorders, accompanied by respiratory manifestations and hypothyroidism. The boy was treated with oral dopasehydrazine to relieve tremor and levothyroxine sodium tablets to relieve hypothyroidism. Anti-infection, atomization, rehabilitation training and other symptomatic supporting treatment were also administered. The boy's language and movement have improved, the thyroid hormone level is normal, and there are still repeated respiratory tract infections.
Athetosis/genetics* ; Chorea ; Congenital Hypothyroidism/genetics* ; Cough ; Humans ; Male ; Respiratory Distress Syndrome, Newborn ; Thyroid Nuclear Factor 1/genetics*

OBJECTIVETo detect potential mutation of immunoglobulin μ -binding protein 2 (IGHMBP2) gene in a two-year-old patient with spinal muscular atrophy with respiratory distress type 1 (SMARD1).

METHODSGenomic DNA was extracted from peripheral blood sample from the patient and her parents, as well as cord blood sample from the fetus. Potential mutations of the coding region of the IGHMBP2 gene was detected with PCR and Sanger sequencing.

RESULTSA heterozygous missense mutation c.1060G>A and a frameshift mutation c.2356delG was detected in the patient. The mutations were respectively inherited from her father and mother. Neither mutation was found in DNA derived from the cord blood sample.

CONCLUSIONThe missense mutation c.1060G>A and frameshift mutation c.2356delG were probably causative for the disease. Analysis of the IGHMBP2 gene has provided an important clue for the etiology and prenatal diagnosis of SMARD1.

Adult ; Base Sequence ; Child, Preschool ; DNA Mutational Analysis ; DNA-Binding Proteins ; genetics ; Female ; Humans ; Infant ; Male ; Molecular Sequence Data ; Muscular Atrophy, Spinal ; genetics ; Pregnancy ; Prenatal Diagnosis ; Respiratory Distress Syndrome, Newborn ; genetics ; Transcription Factors ; genetics

OBJECTIVETo detect and analyze the genetic variation in exon 7 of lung surfactant protein B (SP-B), and to investigate the relationship between the genetic variation and the incidence of neonatal respiratory distress syndrome (NRDS) in Han populations in western Inner Mongolia.

METHODSIn the case-control study, 47 Han infants with NRDS were assigned to case group. All the 47 patients had the last three generations of their ancestors reside in western Inner Mongolia. Forty-seven Han newborns without NRDS were assigned to control group. PCR-based gene analysis was used to determine the mutation in exon 7 of SP-B gene and genotype and allele frequencies of the R236C site in exon 7 of SP-B gene.

RESULTSIn Han newborns in western Inner Mongolia, there was no mutation in exon 7 of SP-B gene; two genotypes, CC and CT, were identified in the R236C site in exon 7 of SP-B gene. No TT genotype was found in the two groups. There were no significant differences in the genotype frequency of CC or CT as well as the allele frequency of C or T between the case and control groups (CC: 72% vs 85%, P>0.05; CT: 28% vs 15%, P>0.05; C: 85% vs 93%, P>0.05; T: 15% vs 7%, P>0.05).

CONCLUSIONSThere is no mutation in exon 7 of SP-B gene in Han infants with NRDS in western Inner Mongolia. There is no significant association between the gene polymorphism of the R236C site in exon 7 of SP-B gene and the incidence of NRDS in Han populations in that region.

Case-Control Studies ; China ; Exons ; Female ; Genotype ; Humans ; Infant, Newborn ; Male ; Polymorphism, Genetic ; Pulmonary Surfactant-Associated Protein B ; genetics ; Respiratory Distress Syndrome, Newborn ; genetics

PURPOSE: Pulmonary surfactant (PS) replacement has been the gold standard therapy for neonatal respiratory distress syndrome; however, almost all commercial PSs contain animal proteins. We prepared a synthetic PS by using a human surfactant protein (SP) analog and evaluated its in vitro properties. MATERIALS AND METHODS: A peptide sequence (CPVHLKRLLLLLLLLLLLLLLLL) of human SP-C was chosen to develop the peptide analog (SPa-C). The new synthetic SP-C PS (sSP-C PS) was synthesized from SPa-C, dipalmitoyl phosphatidylcholine, phosphatidyl glycerol, and palmitic acid. Physical properties of the sSP-C PS were evaluated by measuring the maximum and minimum surface tensions (STs), surfactant spreading, and adsorption rate. In addition, we recorded an ST-area diagram. The data obtained on sSP-C PS were subsequently compared with those of purified natural bovine surfactant (PNBS), and the commercial product, Surfacten(R). RESULTS: The sSP-C PS and Surfacten(R) were found to have maximum ST values of 32-33 mN/m, whereas that of PNBS was much lower at 19 mN/m. The minimum ST values of all three products were less than 10 mN/m. The values that were measured for the equilibrium ST of rapidly spreading sSP-C PS, Surfacten(R), and PNBS were 27, 27, and 24 mN/m, respectively. The surface adsorptions were found to be the same for all three PSs (20 mN/m). ST-area diagrams of sSP-C PS and Surfacten(R) revealed similar properties. CONCLUSION: In an in vitro experiment, the physical properties exhibited by sSP-C PS were similar to those of Surfacten(R). Further study is required to evaluate the in vivo efficacy.
1,2-Dipalmitoylphosphatidylcholine/analogs & derivatives ; Adsorption ; Amino Acid Sequence/*genetics ; Animals ; C-Peptide/*chemistry ; Cattle ; Humans ; Infant, Newborn ; Pulmonary Surfactant-Associated Protein C/*chemical synthesis/pharmacology ; Pulmonary Surfactants/*chemical synthesis/pharmacology ; Respiratory Distress Syndrome, Newborn/*drug therapy ; *Surface Properties ; *Surface Tension ; Surface-Active Agents

OBJECTIVETo investigate the association of ATP-binding cassette transporter A3 (ABCA3) gene mutations with severe neonatal respiratory distress syndrome (NRDS) and lung disease in children.

METHODThirty-eight children hospitalized with respiratory disorders in Children's Hospital of Chongqing Medical University from January 2010 to December 2011 were screened. Two mutations (E292V, G1221S) in the ABCA3 gene were identified. Interstitial lung disease (ILD) was present in 10 cases, NRDS was found in 23 and congenital pulmonary dysplasia in 5 cases. There were 24 males and 14 females, with an age range of 1 hour to 15 years. Genomic DNA was prepared from blood samples and sequences were analyzed by polymerase chain reaction (PCR). Clinical feature, imaging characteristics and the results of gene detection were retrospectively analyzed.

RESULTFour cases with ABCA3 gene mutations were found; 2 patients (case 2 and case 4) had the heterozygous mutation of ABCA3 E292V. One was a 3-hour-old girl and another was a 52-day-old boy, 2 patients (case 1 and case 4) had the heterozygous mutation of ABCA3 G1221S. One was a 78-day-old boy and another was a girl, 15 years and one month old. The family history was negative for respiratory disease. Three patients (case 1, 2, 4 ) had NRDS and 2 (case 1, 2) of them were premature. One patient (case 3) had normal growth and development. She was diagnosed clinically as interstitial lung disease (ILD) after admission. The clinical outcomes of 4 cases were various. Case 1 had recurrent wheezing and inhaled corticosteroid was needed. Case 2 died because she failed to wean from mechanical ventilator. Case 3 was discharged with improvement but lost to follow-up. Case 4 grows normally.

CONCLUSIONGenetic variants within ABCA3 may be the genetic causes or background of a contributor to some unexplained refractory NRDS, and chronic lung disease developed in latter childhood. Identification of ABCA3 genetic variants in NRDS infants is important to offer genetic counseling, as well as early prognosis estimation and intervention in pediatric chronic lung disease.

ATP-Binding Cassette Transporters ; genetics ; Adolescent ; Child ; Child, Preschool ; DNA Mutational Analysis ; Exons ; Female ; Heterozygote ; Humans ; Infant ; Infant, Newborn ; Lung ; diagnostic imaging ; pathology ; Lung Diseases, Interstitial ; diagnosis ; genetics ; Male ; Mutation ; genetics ; Radiography ; Respiratory Distress Syndrome, Newborn ; diagnosis ; genetics

ATP-Binding Cassette Transporters ; genetics ; metabolism ; Animals ; Biological Transport ; Child ; DNA Mutational Analysis ; Humans ; Hypertension, Pulmonary ; genetics ; metabolism ; Lung Diseases, Interstitial ; genetics ; metabolism ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; Protein Conformation ; Pulmonary Surfactant-Associated Proteins ; genetics ; metabolism ; Respiratory Distress Syndrome, Newborn ; genetics ; metabolism

OBJECTIVETo explore the prevalence of pulmonary surfactant associated pathway genes functional variants in Chinese population.

METHODUsing a cohort of 258 mixed ethnic population of Han and Zhuang, we pooled DNA samples from 146 term male infants and 112 term female infants and then used an Ill umina next generation sequencing platform to perform the complete exonic resequencing in 6 target genes:surfactant protein-B (SFTPB), surfactant protein-C (SFTPC), ATP-binding cassette transporter A3 (ABCA3), lysophospholipid acyltransferase 1 (LPCAT1), choline phosphotransferase 1 (CHPT1), phosphate cytidylyltransferase 1, choline, beta (PCYT1B). Collapsing methods was used to determine the functional allele frequency.

RESULT(1) Altogether, 128 variants were found, including 44 synonymous variants, 66 nonsynonymous variants and 18 insertions-deletions. Of these, 28 variants were predicted to alter protein function. Two of these variants were seen twice, the rest variants were only seen once, for a total of 30 functional alleles; (2) ABCA3 had the most functional variants in both male and female groups with the minor allele frequencies of 0.014 (1.4%) and 0.04 (4%), respectively. The total functional allele frequencies of 6 genes were 0.041 (4.1%) and 0.08 (8%) in the two groups, respectively (P = 0.06).

CONCLUSION(1) Functional variants in pulmonary surfactant associated pathway genes are present in the mixed Han-Zhuang population. (2) ABCA3 contained the most functional variants suggesting that ABCA3 could contribute significantly to neonatal respiratory distress syndrome and other lung disease.

1-Acylglycerophosphocholine O-Acyltransferase ; genetics ; metabolism ; ATP-Binding Cassette Transporters ; genetics ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Female ; Gene Frequency ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genetic Variation ; Genotype ; Humans ; Infant, Newborn ; Male ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactant-Associated Proteins ; genetics ; Respiratory Distress Syndrome, Newborn ; ethnology ; genetics

OBJECTIVETo detect possible relationship between genetic defect within the gene encoding member A3 of the ATP Binding Cassette family (ABCA3) and neonatal respiratory distress syndrome (NRDS), thus to understand the genetic mechanisms of NRDS in Han ethnic group.

METHODThe clinical data of 11 cases with NRDS hospitalized in neonatal intensive care unit was investigated. Blood samples were collected from 11 cases with NRDS and 97 unassociated normal individuals. Polymerase chain reaction (PCR) and DNA direct sequencing were performed to screen all exons and their flanking introns of ABCA3 gene for mutation analysis in 11 cases with NRDS. If a new missense variation was identified, single strand conformation polymorphism analysis was performed in 97 healthy controls. Lung tissue sample from a case who died 12 hours after birth was examined with light microscopy and electron microscopy.

RESULTThree missense genetic variants in exons, which include c. 2169 G > A (p.M723I), c. 1010 T > G (p.V337G), c. 4972 A > G (p.S1658G), one splice junction site variation (Exon 30 + 2 T/G), several unreported polymorphism sites [213 C > T(p.F71F), exon 21 + 34C/T] and reported polymorphism site (p.F353F) were identified on ABCA3 gene coding region in 11 case. The homozygous variation (c.2169G > A), which was in exon 17 and causes an M723I amino acid change, was found in the case who died 13 hours after birth, but not detected in 97 controls, indicating that this variation is indeed a mutation and not a polymorphism. In the case carrying c.2169G > A, ultrastructural examination of the alveolar type II cells with electron microscopy demonstrated abnormally small and dense lamellar body with eccentrically distributed electron dense substance.

CONCLUSIONGenetic variants within ABCA3 may be the genetic cause of or a contributor to some unexplained refractory NRDS. Identification of ABCA3 genetic variant in NRDS infants is important to establish appropriate management and evaluation of treatment options, as well as to offer genetic counseling and prenatal diagnosis.

ATP-Binding Cassette Transporters ; genetics ; DNA Mutational Analysis ; Exons ; Humans ; Infant, Newborn ; Polymorphism, Genetic ; Respiratory Distress Syndrome, Newborn ; etiology ; genetics

OBJECTIVETo study the relationship between pulmonary surfactant-associated protein B (SP-B) gene polymorphisms and their susceptibility to neonatal respiratory distress syndrome (RDS).

METHODSEighty-eight preterm infants with RDS (RDS group) and 103 infants without RDS (control group) were enrolled. The genomic DNA was isolated using DNA kits. Polymerase chain reaction with restriction fragment length polymorphism technique was used to detect the genotype and allele frequency of the SP-B -18A/C and SP-B 1580C/T single nucleotide polymorphisms. The association between the polymorphisms and RDS was analyzed.

RESULTSSP-B -18A/C and SP-B 1580C/T were found to be polymorphic in both RDS and control groups. The frequencies of CC genotype (X2=12.26, P<0.01) and C allele (X2=11.97, P<0.01) of SP-B 1580C/T were significantly higher in the RDS group than in the control group. The C allele significantly increased the risk of RDS (OR=2.26, 95%CI: 1.42-3.60). The frequencies of genotype and allele of SP-B -18A/C showed no significant difference between the two groups.

CONCLUSIONSSP-B 1580C/T polymorphism contributes to the etiology of RDS and may serve as the susceptibility gene for RDS. The C allele increases the risk of RDS. SP-B -18A/C shows no association with the etiology of RDS.

Genetic Predisposition to Disease ; Genotype ; Humans ; Infant, Newborn ; Polymorphism, Single Nucleotide ; Pulmonary Surfactant-Associated Protein B ; genetics ; Respiratory Distress Syndrome, Newborn ; etiology ; genetics