Nutritional and health effects of bovine colostrum in neonates.

High concentrations of immunoglobulins, bioactive peptides, and growth factors are found in bovine colostrum (BC), the milk produced by cows in the first few days after parturition. Various biological functions make it increasingly used to provide nutritional support and immune protection to the offspring of many species, including humans. These biological functions include cell growth stimulation, anti-infection, and immunomodulation. The primary components and biological functions of colostrum were reviewed in the literature, and the authors also looked at its latent effects on the growth and development of neonates as well as on conditions such as infections, necrotizing enterocolitis, short bowel syndrome, and feeding intolerance. The importance of BC in neonatal nutrition, immune support, growth and development, and gut health has been demonstrated in a number of experimental and animal studies. BC has also been shown to be safe at low doses without adverse effects in newborns. BC supplementation has been shown to be efficient in preventing several disorders, including rotavirus diarrhea, necrotizing enterocolitis, and sepsis in animal models of prematurity and some newborn studies. Therefore, BC supplementation should be considered in cases where maternal milk is insufficient or donor milk is unavailable. The optimal age, timing, dosage, and form of BC administration still require further investigation.

A neonatal case report of branchiooculofacial syndrome caused by a novel mutation in the TFAP2A gene and literature review.

RATIONALE: Branchiooculofacial syndrome (BOFS) is a rare autosomal dominant disorder with a diverse clinical phenotype. To summarise the clinical characteristics and genetic variations of neonatal-onset BOFS through a case study and literature review. PATIENT CONCERNS: A preterm neonate with a very low birth weight, born at a gestational age of 29+3 weeks, exhibited cosmetic abnormalities at a postmenstrual age of 34+6 weeks, including microcleft lip, high arched palate, curved upper lip, low ear position, and ocular hypertelorism. Hence, a genetic test on peripheral blood was carried out. DIAGNOSES: The genetic testing showed a heterozygous variant of c.724G > A (p.Glu242Lys) in the exon 4 region of the TFAP2A (transcription factor AP-2-α) gene in the short arm of chromosome 6. BOFS was confirmed based on clinical appearance and the genetic result. INTERVENTIONS: The patient underwent solely cleft lip repair at the age of 6 months with no further intervention. OUTCOMES: The infant shows normal growth and development at 1 year of age and subsequent follow-up. LESSONS: The characteristic facial features, branchial skin defects, and ocular anomalies are the main clinical manifestations of BOFS with neonatal onset, but the diverse clinical phenotype and variable genetic variants pose certain challenges for clinical diagnosis.

Down-regulation of the mitochondrial fusion protein Opa1/Mfn2 promotes cardiomyocyte hypertrophy in Su5416/hypoxia-induced pulmonary hypertension rats.

BACKGROUND: Maladaptive right ventricular (RV) remodeling is the most important pathological feature of pulmonary hypertension (PH), involving processes such as myocardial hypertrophy and fibrosis. A growing number of studies have shown that mitochondria-associated endoplasmic reticulum membranes (MAMs) are involved in various physiological and pathological processes, such as calcium homeostasis, lipid metabolism, inflammatory response, mitochondrial dynamics, and autophagy/mitophagy. The abnormal expression of MAMs-related factors is closely related to the occurrence and development of heart-related diseases. However, the role of MAM-related factors in the maladaptive RV remodeling of PH rats remains unclear. METHODS AND RESULTS: We first obtained the transcriptome data of RV tissues from PH rats induced by Su5416 combined with hypoxia treatment (SuHx) from the Gene Expression Omnibus (GEO) database. The results showed that two MAMs-related genes (Opa1 and Mfn2) were significantly down-regulated in RV tissues of SuHx rats, accompanied by significant up-regulation of cardiac hypertrophy-related genes (such as Nppb and Myh7). Subsequently, using the SuHx-induced PH rat model, we found that the downregulation of mitochondrial fusion proteins Opa1 and Mfn2 may be involved in maladaptive RV remodeling by accelerating mitochondrial dysfunction. Finally, at the cellular level, we found that overexpression of Opa1 and Mfn2 could inhibit hypoxia-induced mitochondrial fission and reduce ROS production in H9c2 cardiomyocytes, thereby retarded the progression of cardiomyocyte hypertrophy. CONCLUSIONS: The down-regulation of mitochondrial fusion protein Opa1/Mfn2 can accelerate cardiomyocyte hypertrophy and then participate in maladaptive RV remodeling in SuHx-induced PH rats, which may be potential targets for preventing maladaptive RV remodeling.

Cerebellin-2 promotes endothelial-mesenchymal transition in hypoxic pulmonary hypertension rats by activating NF-κB/HIF-1α/Twist1 pathway.

AIMS: Endothelial-mesenchymal transition (EndMT) is one of the critical factors leading to vascular remodeling in pulmonary hypertension (PH). Recent studies found that the expression of Cerebellin-2 (CBLN2) is significantly increased in the lung tissue of patients with PH, suggesting that CBLN2 may be closely related to the development of PH. This study aims to investigate the role and potential mechanism of CBLN2 in the hypoxia-induced EndMT of PH rats. MATERIAL AND METHODS: Hypoxia-induced PH rat model or EndMT cell model was constructed to investigate the role of CBLN2 in the process of endothelial mesenchymal transition during PH. The effects of CBLN2 siRNA, KC7F2 (HIF-1α inhibitor), and PDTC (NF-κB inhibitor) on hypoxia-induced EndMT were observed to evaluate the potential mechanism of CBLN2 in promoting EndMT. KEY FINDINGS: The right ventricular systolic pressure and pulmonary vascular remodeling index in hypoxia-treated rats were significantly increased. The transformation of endothelial cells (marked by CD31) to mesenchymal cells (marked by α-SMA) can be observed in the pulmonary vessels of PH rats, and the expression of CBLN2 in the intima was also significantly up-regulated. In the hypoxia-induced HPAECs, endothelial cell markers such as VE-cadherin and CD31 expression were significantly down-regulated, while mesenchymal-like cell markers such as α-SMA and vimentin were increased considerably, along with the increased expressions of CBLN2, p-p65, HIF-1α, and Twist1; CBLN2 siRNA, PDTC, and KC7F2 could inhibit those phenomena. SIGNIFICANCE: CBLN2 can promote EndMT by activating NF-κB/HIF-1α/Twist1 pathway. Therefore, CBLN2 may be a new therapeutic target for PH.

Analysis of Anti-Infective Treatment of 9 Neonates with Raoultella ornithinolytica Sepsis.

Raoul ornithine-releasing bacteria widely exist in water, plants, and soil, and colonize the digestive tract and upper respiratory tract of the human body. They are aerobic, unpowered, and capsular opportunistic pathogens. The infectivity of this bacterium is still uncertain, but the possibility of nosocomial infection has been mentioned in the literature. Studies have pointed out that the bacterium should be diagnosed in time and sensitive antibiotics should be used early. Once complicated with sepsis, it can cause multiple organ failure with a poor prognosis. In this study, we retrospectively analyzed the clinical data of nine cases of neonatal L. ornithine septicemia, to explore the clinical characteristics of neonatal L. ornithine septicemia and anti-infection therapy.

Evaluating the therapeutic role of selected active compounds in Plumula Nelumbinis on pulmonary hypertension via network pharmacology and experimental analysis.

Excessive proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) are critical factors leading to vascular remodeling in pulmonary hypertension (PH). This study aimed to explore the effect and potential mechanism of Plumula Nelumbinis on PH by using network pharmacology and experimental analysis. Network pharmacology and molecular docking results indicated that the potential active components of Plumula Nelumbinis against PH were mainly alkaloid compounds, including neferine, liensinine, and isoliensinine. Subsequently, by constructing a Su5416 plus hypoxia (SuHx)-induced PH rat model, we found that the total alkaloids of Plumula Nelumbinis (TAPN) can reduce the right ventricular systolic pressure, delay the process of pulmonary vascular and right ventricular remodeling, and improve the right heart function in PH rats. In addition, TAPN can effectively reverse the upregulation of collagen1, collagen3, MMP2, MMP9, PCNA, PIM1, and p-SRC protein expression in lung tissue of PH rats. Finally, by constructing a hypoxia-induced PASMCs proliferation and migration model, we further found that TAPN, neferine, liensinine, and isoliensinine could inhibit the proliferation and migration of PASMCs induced by hypoxia; reverse the upregulation of collagen1, collagen3, MMP2, MMP9, PCNA, PIM1 and p-SRC protein expression in PASMCs. Based on these observations, we conclude that the alkaloid compounds extracted from Plumula Nelumbinis (such as neferine, liensinine, and isoliensinine) can inhibit the abnormal proliferation and migration of PASMCs by regulating the expression of p-SRC and PIM1, thereby delaying the progression of PH.

ZPA Regulatory Sequence Variants in Chinese Patients With Preaxial Polydactyly: Genetic and Clinical Characteristics.

Preaxial polydactyly (PPD) is a common congenital abnormality with an incidence of 0.8-1.4% in Asians, characterized by the presence of extra digit(s) on the preaxial side of the hand or foot. PPD is genetically classified into four subtypes, PPD type I-IV. Variants in six genes/loci [including GLI family zinc finger 3 (GLI3), ZPA regulatory sequence (ZRS), and pre-ZRS region] have been identified in PPD cases. Among these loci, ZRS is, perhaps, the most special and well known, but most articles only reported one or a few cases. There is a lack of reports on the ZRS-variant frequency in patients with PPD. In this study, we recruited 167 sporadic or familial cases (including 154 sporadic patients and 13 families) with PPD from Central-South China and identified four ZRS variants in four patients (2.40%, 4/167), including two novel variants (ZRS131A > T/chr7:g.156584439A > T and ZRS474C > G/chr7:g.156584096C > G) and two known variants (ZRS428T > A/chr7:g.156584142T > A and ZRS619C > T/chr7:g.156583951C > T). ZRS131A > T and ZRS428T > A were detected in PPD I cases and ZRS474C > G and ZRS619C > T combinedly acted to cause PPD II. The detectable rate of ZRS variants in PPD I was 1.60% (2/125), while PPD II was significantly higher (9.52%, 2/21). Three bilateral PPD cases harbored ZRS variants (13.64%, 3/22), suggesting that bilateral PPD was more possibly caused by genetic etiologies. This study identified two novel ZRS variants, further confirmed the association between ZRS and PPD I and reported a rare PPD II case resulted from the compound heterozygote of ZRS. This investigation preliminarily evaluated a ZRS variants rate in patients with PPD and described the general picture of PPD in Central-South China.

Magnolol alleviates hypoxia-induced pulmonary vascular remodeling through inhibition of phenotypic transformation in pulmonary arterial smooth muscle cells.

Phenotypic transformation and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) play an important role in vascular remodeling during pulmonary hypertension (PH). Magnolol (5,5'-diallyl-2,2'-dihydroxybiphenyl) is the major bioactive constituent isolated from the bark of Magnolia Officinalis, which has anti-inflammatory, antioxidant, and cardiovascular protection effects. However, the effect of magnolol on the phenotypic transformation of PASMCs is still unknown. This study aims to evaluate the effects of magnolol on the phenotypic transformation of PASMCs induced by hypoxia. In vivo, Sprague Dawley rats were exposed to hypoxia (10% O2) for four weeks to establish a PH model. The results showed that hypoxia treatment led to an increase in right ventricle systolic pressure, Fulton index, collagen production, accompanied by upregulation in the expression of collagen Ⅰ, collagen Ⅲ, OPN, PCNA, CyclinD1, p-JAK2, and p-STAT3, as well as decreases in expression of SM-22α; these changes were attenuated by magnolol. In vitro, the primary cultured PASMCs were exposed to 3% O2 for 48 h to induce phenotypic transformation. Consistent with the findings in vivo, magnolol treatment could prevent the phenotypic transformation and hyperproliferation of PASMCs induced by hypoxia, accompanied by downregulation in the expression of p-JAK2 and p-STAT3. In summary, this study demonstrated that the protective effect of magnolol on PH vascular remodeling is related to the inhibition of phenotypic transformation and hyperproliferation of PASMCs by inhibiting the JAK2/STAT3 pathway.

The Diagnosis and Management of Allergic Reactions Caused by Chinese Materia Medica.

Traditional Chinese medicines (TCM) have been used in China for thousands of years. Although TCM has been generally perceived to be safe, adverse reactions to Chinese materia medica (CMM) have been reported. Most of the adverse reactions are allergic in nature, but other mechanisms may play a role. This review focuses on the mechanism and clinical presentation of these allergic reactions. Allergic reactions can occur as a result of the active and inactive ingredients of CMM. Impurities and chemicals generated during the production process can also lead to allergic or adverse reactions. Environmental factors such as temperature, humidity, and light can cause changes in the allergenicity of drugs. Human error in formulating CMM drugs also contributes to adverse drug reactions. The management of allergic reactions to CMM includes taking a good history, avoidance of medications in the same class as those which caused prior reactions, the proper training of staff, adherence to manufacturer guidelines and expiration dates, evaluation of benefit and risk balance, and the formulation of a risk management strategy for the use of CMM. A small test dose of a considered drug before using, improvements in drug purification technology, and proper storage and clinical administration help reduce allergic reactions due to CMM.

A Novel Homozygous Variant of TMEM231 in a Case With Hypoplasia of the Cerebellar Vermis and Polydactyly.

Background: Transmembrane protein 231 (TMEM231) is a component of the B9 complex that participates in the formation of the diffusion barrier between the cilia and plasma membrane. Mutations in TMEM231 gene may contribute to the Joubert syndrome (JBTS) or Meckel-Gruber syndrome (MKS). However, reports on JBTS or MKS caused by TMEM231 mutations are comparatively rare. Method: We describe a Chinese fetus with unexplained hypoplasia of the cerebellar vermis and polydactyly, detected by ultrasound imaging. The fetus was primarily diagnosed with JBTS/MKS. The parents of this fetus were non-consanguineous and healthy. Whole-exome sequencing (WES) and bioinformatics strategies were employed to explore the genetic lesion of this family. Results: An unknown missense variant (c.19C>T;p.R7W) of TMEM231 gene was detected. The variant was predicted as pathogenic and was absent in our 200 healthy controls. Conclusion: WES was employed to explore the genetic lesion of a fetus with unexplained hypoplasia of the cerebellar vermis and polydactyly. A novel variant in TMEM231 gene was identified. Our study not only provided data for genetic counseling and prenatal diagnosis to this family but also broadened the spectrum of TMEM231 mutations.

Magnolol Attenuates Right Ventricular Hypertrophy and Fibrosis in Hypoxia-Induced Pulmonary Arterial Hypertensive Rats Through Inhibition of the JAK2/STAT3 Signaling Pathway.

Right ventricular (RV) remodeling is one of the essential pathological features in pulmonary arterial hypertension (PAH). RV hypertrophy or fibrosis are the leading causes of RV remodeling. Magnolol (6, 6', 7, 12-tetramethoxy-2,2'-dimethyl-1-ß-berbaman, C18H18O2) is a compound isolated from Magnolia Officinalis. It possesses multiple pharmacological activities, such as anti-oxidation and anti-inflammation. This study aims to evaluate the effects and underlying mechanisms of magnolol on RV remodeling in hypoxia-induced PAH. In vivo, male Sprague Dawley rats were exposed to 10% O2 for 4 weeks to establish an RV remodeling model, which showed hypertrophic and fibrotic features (increases of Fulton index, cellular size, hypertrophic and fibrotic marker expression), accompanied by an elevation in phosphorylation levels of JAK2 and STAT3; these changes were attenuated by treating with magnolol. In vitro, the cultured H9c2 cells or cardiac fibroblasts were exposed to 3% O2 for 48 h to induce hypertrophy or fibrosis, which showed hypertrophic (increases in cellular size as well as the expression of ANP and BNP) or fibrotic features (increases in the expression of collagen Ⅰ, collagen Ⅲ, and α-SMA). Administration of magnolol and TG-101348 or JSI-124 (both JAK2 selective inhibitors) could prevent myocardial hypertrophy and fibrosis, accompanied by the decrease in the phosphorylation level of JAK2 and STAT3. Based on these observations, we conclude that magnolol can attenuate RV hypertrophy and fibrosis in hypoxia-induced PAH rats through a mechanism involving inhibition of the JAK2/STAT3 signaling pathway. Magnolol may possess the potential clinical value for PAH therapy.

Case Report: A Novel Heterozygous Mutation of CD2AP in a Chinese Family With Proteinuria Leads to Focal Segmental Glomerulosclerosis.

Idiopathic focal segmental glomerulosclerosis (FSGS) is a relatively frequent kidney disorder that manifest clinically as proteinuria and progressive loss of renal function. Genetic factors play a dominant role in the occurrence of FSGS. CD2-associated protein (CD2AP) is an adapter molecule and is essential for the slit-diaphragm assembly and function. Mutations in the CD2AP gene can contribute to FSGS development. Here, we describe a Chinese family of four generations with unexplained proteinuria. The proband, a 12-year-old boy, was diagnosed as FSGS. Whole-exome sequencing (WES) revealed an unknown frameshift insertion mutation (p.K579Efs*7) of CD2AP gene that leads to a truncation of CD2AP protein. Bioinformatics strategies predicted that the novel mutation was pathogenic. The mutation was absent in either healthy family members or our 200 healthy controls. In summary, we used WES to explore the genetic lesion of FSGS patients and identified a novel mutation in CD2AP gene. This work broadens the mutation spectrum of CD2AP gene and provides data for genetic counseling to additional FSGS patients.

Case Report: Exome Sequencing Identified a Novel Frameshift Mutation of α-Actin 1 in a Chinese Family With Macrothrombocytopenia and Mild Bleeding.

Inherited macrothrombocytopenia (IMTP) is a rare disorder characterized by a reduced platelet count and abnormally large platelets. The main clinical symptom of IMTP is mild bleeding in some patients. At present, more than 30 genes have been identified in patients with syndromic and non-syndromic IMTP. In this study, a 3-year-old boy and his mother who presented with mild epistaxis and/or gingival bleeding were diagnosed as having IMTP. Wen then selected whole sequencing to explore the genetic lesion of the patients. After data filtering and mutation validation, a novel frameshift mutation (NM_001130004: c.398_399insTGCG, p.F134AfsX60) of α-actin 1 (ACTN1) was identified in the proband and his mother but absent in other unaffected individuals. Previous studies have proven that mutations in ACTN1 may lead to IMTP with mild to absent bleeding phenotype. The novel mutation, resulting in a truncated protein in exon 4 of the ACTN1 gene, was absent in the public database, such as 1000G and genomAD. Further Western blot revealed that the expression of α-actin 1 in the proband was decreased overtly, which indicated that the novel frameshift mutation may induce non-sense-mediated mRNA decay. In summary, this study not only broadened the variants spectrum of ACTN1 gene, which may contribute to the genetic counseling of IMTP, but also confirmed the diagnosis of IMTP, which may help the management and prognosis for the family members.

Corrigendum: Case Report: Chorea-Acanthocytosis Presents as Epilepsy in a Consanguineous Family With a Nonsense Mutation of in VPS13A.

[This corrects the article DOI: 10.3389/fnins.2021.604715.].

Case Report: Chorea-Acanthocytosis Presents as Epilepsy in a Consanguineous Family With a Nonsense Mutation of in VPS13A.

Chorea-Acanthocytosis (ChAc), a rare autosomal recessive inherited neurological disorder, originated from variants in Vacuolar Protein Sorting 13 homolog A (VPS13A) gene. The main symptoms of ChAc contain hyperkinetic movements, seizures, cognitive impairment, neuropsychiatric symptoms, elevated serum biochemical indicators, and acanthocytes detection in peripheral blood smear. Recently, researchers found that epilepsy may be a presenting and prominent symptom of ChAc. Here, we enrolled a consanguineous family with epilepsy and non-coordinated movement. Whole exome sequencing was employed to explore the genetic lesion of the family. After data filtering, co-separation analysis was performed by Sanger sequencing and bioinformatics analysis, the homozygous nonsense variant (NM_033305.2: c.8282C>G, p.S2761X) of VPS13A were identified which could be genetic factor of the patient. No other meaningful mutations were detected. This mutation (p.S2761X) led to a truncated protein in exon 60 of the VPS13A gene, was simultaneously absent in our 200 local control participants. The homozygous mutation (NM_033305.2: c.8282C>G, p.S2761X) of VPS13A may be the first time be identified in ChAc patient with epilepsy. Our study assisted to the diagnosis of ChAc in this patient and contributed to the genetic diagnosis and counseling of families with ChAc presented as epilepsy. Moreover, we further indicated that epilepsy was a crucial phenotype in ChAc patients caused by VPS13A mutations.

GLIS Family Zinc Finger 1 was First Linked With Preaxial Polydactyly I in Humans by Stepwise Genetic Analysis.

Background: Preaxial polydactyly (PPD) is one of the most common developmental malformations, with a prevalence of 0.8-1.4% in Asians. PPD is divided into four types, PPD I-IV, and PPD I is the most frequent type. Only six loci (GLI1, GLI3, STKLD1, ZRS, pre-ZRS, and a deletion located 240 kb from SHH) have been identified in non-syndromic PPD cases. However, pathogenesis of most PPD patients has never been investigated. This study aimed to understand the genetic mechanisms involved in the etiology of PPD I in a family with multiple affected members. Methods: We recruited a PPD I family (PPD001) and used stepwise genetic analysis to determine the genetic etiology. In addition, for functional validation of the identified GLIS1 variant, in vitro studies were conducted. GLIS1 variants were further screened in additional 155 PPD cases. Results: We identified a GLIS1 variant (NM_147193: c.1061G > A, p.R354H) in the PPD001 family. In vitro studies showed that this variant decreased the nuclear translocation of GLIS1 and resulted in increased cell viability and migration. RNA sequencing revealed abnormal TBX4 and SFRP2 expression in 293T cells transfected with mutant GLIS1. Additionally, we identified a GLIS1 variant (c.664G > A, p.D222N) in another PPD case. Conclusion: We identified two GLIS1 variants in PPD I patients and first linked GLIS1 with PPD I. Our findings contributed to future molecular and clinical diagnosis of PPD and deepened our knowledge of this disease.

Variation in IgE binding potencies of seven Artemisia species depending on content of major allergens.

BACKGROUND: Artemisia weed pollen allergy is important in the northern hemisphere. While over 350 species of this genus have been recorded, there has been no full investigation into whether different species may affect the allergen diagnosis and treatment. This study aimed to evaluate the variations in amino acid sequences and the content of major allergens, and how these affect specific IgE binding capacity in representative Artemisia species. METHODS: Six representative Artemisia species from China and Artemisia vulgaris from Europe were used to determine allergen amino acid sequences by transcriptome, gene sequencing and mass spectrometry of the purified allergen component proteins. Sandwich ELISAs were developed and applied for Art v 1, Art v 2 and Art v 3 allergen quantification in different species. Aqueous pollen extracts and purified allergen components were used to assess IgE binding by ELISA and ImmunoCAP with mugwort allergic patient serum pools and individual sera from five areas in China. RESULTS: The Art v 1 and Art v 2 homologous allergen sequences in the seven Artemisia species were highly conserved. Art v 3 type allergens in A. annua and A. sieversiana were more divergent compared to A. argyi and A. vulgaris. The allergen content of Art v 1 group in the seven extracts ranged from 3.4% to 7.1%, that of Art v 2 from 1.0% to 3.6%, and Art v 3 from 0.3% to 10.5%. The highest IgE binding potency for most Chinese Artemisia allergy patients was with A. annua pollen extract, followed by A. vulgaris and A. argyi, with A. sieversiana significantly lower. Natural Art v 1-3 isoallergens from different species have almost equivalent IgE binding capacity in Artemisia allergic patients from China. CONCLUSION AND CLINICAL RELEVANCE: There was high sequence similarity but different content of the three group allergens from different Artemisia species. Choice of Artemisia annua and A. argyi pollen source for diagnosis and immunotherapy is recommended in China.

A novel heterozygous variant of the COL4A4 gene in a Chinese family with hematuria and proteinuria leads to focal segmental glomerulosclerosis and chronic kidney disease.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS), as the frequent primary glomerular diseases in adults, accounts for symptomless proteinuria or nephrotic syndrome with or without renal insufficiency. As the crucial lesion of chronic kidney disease (CKD), accumulating evidence from recent studies show that mutations in Collagen-related genes may be responsible for FSGS. The aim of this study was to identify the genetic lesion of a Chinese family with FSGS and CKD. METHODS: In this study, we recruited a Han-Chinese family with unexplained high serum creatinine, hematuria, and proteinuria. Further renal biopsy and renal pathology indicated the diagnosis of FSGS in the proband. Whole-exome sequencing and Sanger sequencing were employed to explore the pathogenic mutation of this family. RESULTS: A novel heterozygous mutation (NM_000092 c.2030G>A, p.G677D) of the collagen type IV alpha-4 gene (COL4A4) was detected. Co-segregation analysis revealed that the novel mutation was carried by all the five affected individuals and absent in other healthy members as well as in our 200 local control cohorts. Bioinformatics predication indicated that this novel mutation was pathogenic and may disrupt the structure and function of type IV collagen. Simultaneously, this variant is located in an evolutionarily conserved site of COL4A4 protein. CONCLUSION: Here, we identified a novel mutation of COL4A4 in a family with FSGS and CKD. Our study expanded the variants spectrum of the COL4A4 gene and contributed to the genetic counseling and prenatal genetic diagnosis of the family. In addition, we also recommended the new classification of collagen IV nephropathies, which may be a benefit to the diagnosis, target drug treatment, and management of patients with COL4A3/COL4A4 mutations.