Gene Mutations In Chinese Patients Research Articles

Mutational profile evaluates metastatic capacity of Chinese colorectal cancer patients, revealed by whole-exome sequencing

Colorectal cancer (CRC) is the third most common cancer and the prevalence rate of CRC is increasing in the China. In this study, whole-exome sequencing (WES) was performed on primary tissues of 47 CRC Chinese patients including 22 metastatic and 25 non-metastatic patients. By comparison with data from western colorectal cancer patients in the Cancer Genome Atlas (TCGA), we identified a number of genes that are more likely to be mutated in Chinese colorectal cancer patients, such as MUC12, MUC12, MUC2, MUC4, HYDIN and KMT2C. Interestingly, MUC family genes including MUC12, MUC2 and MUC4, have mutation rates of >20%, while the mutation frequency was extremely low in western colorectal cancer patients, which were <3% in TCGA and 0% in Memorial Sloan Kettering Cancer Center (MSKCC). We detected metastasis-specific mutated genes including TCF7L2, MST1L, HRNR and SMAD4, while MUC4, NEB, FLG and RFPL4A alteration is more prevalent in the non-metastasis group. Further analysis reveals mutation genes in metastasis group are more focus in the Wnt and Hippo signaling pathway. APC, SMAD4 and TCF7L2 accounted for the major genetic abnormalities in this pathway. In conclusion, this study identified the unique characteristics of gene mutations in Chinese patients with colorectal cancer, and is a valuable reference for personalized treatment in Chinese CRC patients.

Germline RECQL gene mutations in Chinese patients with breast cancer.

Breast cancer is the most common malignant tumor in women, seriously threatening health and survival. TP-dependent DNA helicase Q1 (RECQL) is a breast cancer susceptibility gene with possible familial links. However, RECQL gene mutations among Chinese women with breast cancer have not been evaluated. Therefore, this study assessed RECQL mutations and their relationships with clinicopathological and epidemiological characteristics in Chinese women with breast cancer. Clinical information was also obtained via the hospital information system and a follow-up questionnaire. Peripheral venous blood (2 mL) was extracted from all patients and stored at -80°C for future use; the early venous blood samples were from our hospital's sample bank. RECQL gene sequencing were performed by the Shanghai Aishe Gene Company (China). We found that a RECQL mutation is a susceptibility factor for breast cancer. Moreover, patients with RECQL mutations were more likely to have a family history of breast cancer than those without. Also, patients with RECQL variants of uncertain significance (VUS) were less likely to develop invasive ductal carcinoma than those without. In addition, unexplained RECQL mutations occurred more often in patients with human epidermal growth factor receptor 2+ breast cancer than in those with other subtypes. These results provide a basis for creating screening criteria specific to Chinese women. However, the frequency of RECQL mutations was low, and the number of pathogenic mutations was too small and could not be analyzed. Thus, more extensive, long-term studies that include other functional experiments are needed to verify these results.

Identification of Arrhythmia-Associated Gene Mutations in Chinese Patients with Primary Electrical Disorders or Sudden Cardiac Death

Background: Sudden cardiac death (SCD), unexpected death based on sudden cardiac ejection cessation, accounts for 15–20% of unnatural deaths in developed countries. Primary electrical disorders (PEDs), a group of cardiac rhythm abnormalities without detectable structural heart disease, are a major cause of SCD in people younger than 35 years of age. Cardiac muscle contraction and relaxation are triggered by the action potential (AP), which is generated by ionic changes across the cell membrane. Thus, PEDs are influenced by mutations in AP-associated genes, such as KCNE1 and RYR2. Methods: We recruited six patients with SCD and 42 patients with arrhythmia with onset under the age of 25, and used targeted sequencing to determine the genetic etiologies. Results: We identified five mutations (RYR2: c.12269C&gt;T, p.P4090L; KCNE1: c.169T&gt;C, p.F57L; KCNQ1: c.853A&gt;C, p.K285Q; KCNH2: c.793T&gt;C, p.C265R, and TRPM4: c.2985_3012del, p.E996Gfs*118) in five families with PED/SCD. Conclusions: We detected five mutations and expanded the mutation spectrum of PED-associated genes, thus contributing to the clinical diagnosis of PED.

Clinical and genetic findings in 13 Chinese children with keratinopathic ichthyosis.

Keratinopathic ichthyosis (KPI) represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the KRT1, KRT2, or KRT10 genes. In KPI, the relationship between genotype and phenotype is complex. To analyze the clinical manifestations and gene mutations in Chinese patients with KPI. Clinical data were collected from 13 children diagnosed with KPI, and peripheral blood DNA samples were extracted from both the patients and their parents Next-generation sequencing was performed using a congenital ichthyosis multi-gene panel, and the selected variants in the patients and their parents were further validated using the Sanger sequencing method. Genetic analysis identified missense mutations in either KRT1 or KRT10 in ten patients exhibiting varying degrees of severity and distinct features of epidermolytic ichthyosis. A missense hotspot mutation in KRT2 was identified in one patient with superficial epidermolytic ichthyosis. Additionally, two truncation mutations in KRT10 were detected, leading to the development of generalized ichthyosiform erythroderma. Ear malformation and ectropion at birth, scalp involvement, and palmoplantar hyperkeratosis were observed as early signs of ichthyosis with confetti. We analyzed the genotype-phenotype correlations in KPI, revealing that the types and locations of different mutations are associated with distinct phenotypic characteristics. Oral acitretin could be considered a treatment option for severe patients at an appropriate dosage and timing.

Identification of GJC2 gene mutations in Chinese patients with Pelizaeus-Merzbacher-like disease.

Clinical and genetic features were analyzed in five pedigrees with Pelizaeus-Merzbacher-like disease (PMLD) to provide bases for genetic counseling and prenatal diagnosis. Six patients from five pedigrees were diagnosed with PMLD based on their clinical data. Six GJC2 novel mutations were found in this study, expanding the spectrum of GJC2 mutations. This is the second group of GJC2 mutations reported from six Chinese patients with PMLD. Clinical data including medical history, physical signs, and auxiliary examinations were collected from six patients and their family numbers in five pedigrees with PMLD. Polymerase chain reaction and sequence analysis were used to amplify GJC2 and PLP1 alterations, while multiplex ligation-dependent probe amplification (MLPA) was performed to detect PLP1 dosage changes. The gene mutations were diagnosed for further analysis of the genetic features. A total of seven GJC2 mutations were identified in these patients, including two novel missense mutations (c.217C>T, p.Pro73Ser; c.1199C>A, p.Ala400Glu), one nonsense mutation (c.735C>A, p.Cys245X), three novel frameshift mutations (c.579delC, p.Gly193fsX17 and c.1296_1297insG, p.Gly433fsX59; c.689delG, p.Gly230AlafsX241), and one known missense mutation (c.814T>G, p.Tyr272Asp). Compound heterozygotes were found for P1-3, while homozygotes were found for P4-6 that were inherited from their parents with normal phenotypes except for P5 and P6, respectively. The c.814T>G (p.Tyr272Asp) mutation in P5 was de novo. A c.1199C>A (p.Ala400Glu) homozygous mutation in GJC2 was identified in P6. A heterozygous variation was found in his father and the wild type was seen in his mother.

Heterogeneous spectrum of CFTR gene mutations in Chinese patients with CAVD and the dilemma of genetic blocking strategy.

The genetic heterogeneity of CFTR gene mutations in Chinese patients with congenital absence of the vas deferens (CAVD) differs from the hotspot mutation pattern in Caucasians. This paper reviews and suggests a more suitable screening strategy for the Chinese considering the dilemma of CFTR genetic blocking. Congenital absence of the vas deferens (CAVD) is a major cause of obstructive azoospermia and male infertility, with CFTR gene mutation as the main pathogenesis. Other genes such as ADGRG2, SLC9A3, and PANK2 have been discovered and proven to be associated with CAVD in recent studies. Multiple CFTR hotspot mutations have been found in Caucasians in several foreign countries, and relevant genetic counseling and preimplantation genetic diagnosis (PGD) have been conducted for decades. However, when we examined research on Chinese CAVD, we discovered that CFTR mutations show heterogeneity in the Chinese Han population, and there is currently no well-established screening strategy. Therefore, we have reviewed the literature, combining domestic and international research as well as our own, aiming to review research progress on the CFTR gene in China and discuss the appropriate scope for CFTR gene detection, the detection efficiency of other CAVD-related genes, and the screening strategy applicable to the Chinese Han population. This study provides more valuable information for genetic counseling and a theoretical basis for PGD and treatment for couples with CAVD when seeking reproductive assistance.

99P Landscape of homologous recombination repair gene mutations in different molecular subtypes of NSCLC

Lung cancer is one of the malignant tumors with high morbidity and mortality in the world. PARP inhibitors have become a new line of cancer therapy The mechanism and efficacy of PARP inhibitors have been well studied in some cancers, especially homologous recombination (HR)-deficient ovarian cancer, and several cell line experiments have shown that HR-deficient lung cancers are sensitive to PARP inhibitor. Meanwhile, HHR gene is a potential biomarker for immunotherapy. Herein, we evaluated the characteristics of HRR related gene mutations in Chinese patients with lung adenocarcinoma (LUAD) or lung squamous cell carcinoma (LUSC).

Analysis of mutations in DNA damage repair pathway gene in Chinese patients with hepatocellular carcinoma

The incidence of hepatocellular carcinoma (HCC) has increased in these years. DNA damage repair (DDR) pathway is required in response to DNA damage Gene mutations in DDR pathway play an important role in different stages of tumorigenesis and development. Based on the importance of DDR pathway in precision therapy of multiple cancers, we analyzed DDR gene mutations in Chinese patients with HCC. The results showed that (tumor mutation burden) TMB was significantly higher in HCC patients who carried somatic mutations in DDR than in non-carriers, and TMB in patients with DS, MMR mutations and DDR genes mutations such as RAD50, MLH1, MSH2, CHEK2 was significantly higher than that in wild-type patients. Based on the results of next-generation sequencing (NGS) testing, we are trying to provide clues for targeted therapy and provide feasible basis for PD-1/PD-L1 immune checkpoint inhibitor therapy.

Correlation between MSI, TMB, and RAS gene mutation in solid tumors.

2624 Background: RAS gene family encodes a protein that is a member of the small GTPase super family and plays an important role in the regulation of cell proliferation and promoting oncogenic events. Studies have reported that RAS gene shows a high mutation frequency in lung cancer, colorectal cancer and pancreatic cancer. However, the relation between RAS-mutant and RAS-wild type tumors in tumor mutation burden (TMB) and microsatellite instability (MSI) remain unclear in pan-cancer. Methods: We retrospectively analyzed 15188 Chinese patients with pan-cancer from laboratory of Simcere Diagnosis (Nanjing, China) during 2019-2021. Somatic mutations in tumor samples were assessed by next-generation sequencing (NGS). We evaluated RAS (KRAS, NRAS and HRAS) mutation frequency, TMB and MSI in RAS-mutant and RAS wild-type tumors. Results: RAS mutations were detected in 2663 (17.5%) samples, including 88.7% of KRAS mutations, 9.1% of NRAS mutations and 3.5% of HRAS mutations. The top 6 frequently cancers were colorectal cancer (829, 31.1%), lung cancer (747, 28.1%), pancreatic cancer (358, 13.4%), biliary tract cancer (210, 7.9%), liver cancer (78, 2.9%), and gastric cancer (73, 2.7%). We found that the incidence of MSI-H in patients with RAS-mutant solid tumors was 3.3% and the frequency of MSI-H was significantly higher in RAS-mutant gastric cancer than that in RAS wild-type (RAS-MUT vs RAS-WT, 20.5% vs 3.5%, p &lt; 0.001). Contrary to our assumption, it was not observed in colorectal cancer (RAS-MUT vs RAS-WT, 5.8% vs 6.9%). In the analysis of TMB, RAS gene mutation was associated with higher TMB (P &lt; 0.01). 27.4% of RAS-mutant gastric cancer and 10.8% RAS wild-type gastric cancer were classified as TMB-H (TMB ≥10 muts/Mb) (P＜0.01), while 13.4% of RAS-mutant colorectal cancer was TMB-H, with no significant difference between RAS wild-type. However, we did not observe a close association between MSI, TMB and RAS gene mutations in lung cancer, pancreatic cancer, biliary tract cancer, and liver cancer. Conclusions: We analyzed RAS gene mutations in Chinese patients with solid tumor. Our data showed that RAS mutations were associated with TMB-H and MSI-H in solid tumors, especially gastric cancer. In colorectal cancer, RAS mutations were associated with higher TMB, but not TMB-H. It was showed that RAS mutations in specific cancer types, such as gastric cancer and colorectal cancer, may be related to the efficacy of immunotherapy.

A Novel SACS Variant Identified in a Chinese Patient: Case Report and Review of the Literature

Mutations in the SACS gene have been linked to autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS). It is a clinically and genetically heterogeneous disease characterized by slow progressive ataxia, spasticity, sensorimotor neuropathy, and a combination of other manifestations, such as lack of spasticity, hearing loss, and epileptic seizures. Currently, there have been very few case reports regarding the SACS gene mutation in Chinese patients. Here, we describe a 35-year-old Chinese patient carrying a novel variant in SACS (c.11486C>T) presenting with progressive ataxia and demyelinating peripheral neuropathy. We then reviewed 22 Chinese cases carrying SACS gene mutations, including our patient. All of them had a cerebellar ataxia gait and showed cerebellar atrophy on brain magnetic resonance imaging (MRI). A total of 28 SACS mutations were identified in these patients. Our study further expands the mutation spectrum of the SACS gene and contributes to the evaluation of genotype-phenotype correlations.

Novel ADAMTSL4 gene mutations in Chinese patients with isolated ectopia lentis

BackgroundTo characterise the phenotype and genetic defects of isolated ectopia lentis (IEL) and to determine the ADAMTSL4 gene mutation frequencies in a Chinese congenital ectopia lentis (CEL) cohort.MethodsIn total, 127...

Mutations in FIGLA Associated With Premature Ovarian Insufficiency in a Chinese Population.

Objective: Premature ovarian insufficiency (POI) is one of the most common reproductive endocrinological causes of infertility in women of child-bearing age. The purpose of this study was to identify FIGLA gene mutations in Chinese patients with POI and to investigate the underlying mechanism.Methods: A total of 113 patients with idiopathic POI and 100 healthy controls were recruited for the analysis of FIGLA variants. Based on the identification of common mutations in the FIGLA, wild-type and mutant plasmids were constructed and transfected into HEK293 cells. Luciferase reporter genes were used to determine the effect of wild-type and mutant FIGLA genotypes on the transcriptional activity of its downstream targets, the zona pellucida glycoprotein genes ZP1, ZP2, and ZP3. Chromatin immunoprecipitation was used to determine the level of binding between wild-type and mutant FIGLA with the ZP1, ZP2, and ZP3 promoters.Results: Three different FIGLA mutations were identified in four patients with POI. Two patients carried the mutation c.11C>A (p.A4E), and the other two patients, respectively, carried the mutations c.625G>A (p.V209I) and c.84C>A (p.D28E). The luciferase reporter assay indicated that ZP1, ZP2, and ZP3 transcriptional activities were significantly reduced in individuals with FIGLA mutations. Chromatin immunoprecipitation indicated that the FIGLA mutation significantly decreased binding with the ZP1, ZP2, and ZP3 promoters.Conclusion: FIGLA mutation affects gene transcriptional regulation of its downstream target genes ZP1, ZP2, and ZP3, highlighting a new candidate genetic factor that causes POI. Our study demonstrates that FIGLA has a regulatory effect on reproduction-specific genes, thereby providing a basis for elucidating the specific regulatory mechanism of FIGLA in germ cell growth and development.

Rare and novel GNAS gene mutations in Chinese patients with thyroid cancer

AbstractBackgroundA large number of novel, rare, and uncharacterized mutations in Tumors including thyroid cancer (TC) have been discovered. In this study, we reported two GNAS mutations in Chinese TC patients, and assessed the functional impact.MethodsTwo hundred and twenty five formalin‐fixed, paraffin‐embedded (FFPE) tissue specimens from Chinese TC patients were tested by NGS. The functional impact of GNAS mutations was assessed using sorting intolerant from tolerant tools (SIFT), polymorphism phenotyping v2 (POLYPHEN‐2) and the mutation assessor. The GNAS protein structure was modeled by Iterative Threading ASSEmbly Refinement (I‐TASSER), and modeling of mutations was performed and visualised by PyMOL.ResultsTwo somatic missense GNAS gene mutations including a rare c.956A&gt;G(p.D319G) and a novel c.1399G&gt;T(p.A467S) were detected in 225 TC tissues (2/225, 0.89%). The novel GNAS mutation c.1399G&gt;T(p.A467S) was predicted to benign and low impact on the protein. SIFT and Mutation Assessor predicted c.956A&gt;G(p.D319G) will be neutral and have low impact, while Polyphen‐2 indicated the mutation may be probably damaging. c.1399G&gt;T(p.A467S) and c.956A&gt;G(p.D319G) molecular modeling data showed two mutations not changed in Gsα, and showed little predicted effect on protein structure.ConclusionsA rare somatic GNAS gene mutations c.956A&gt;G(p.D319G) and a novel somatic GNAS mutation c.1399G&gt;T(p.A467S) were found in the present study, which appeared to be associated with low impact on the protein.

Novel Norrie disease gene mutations in Chinese patients with familial exudative vitreoretinopathy

PurposeThis study aims to analyze the Norrie disease gene (NDP) variants in patients with familial exudative vitreoretinopathy (FEVR) and their clinical features.MethodsThirty-three Chinese patients (22 familial and 11 simplex) who were diagnosed as FEVR underwent detailed ocular examinations in Beijing Tongren Hospital. Peripheral venous blood was drawn from the patients and their family members for the extraction of genomic DNA. All exons of NDP gene were analyzed by direct sequencing of PCR-amplified DNA fragments.ResultsFour novel mutations in NDP gene were identified in four X-linked FEVR families: a C → T transversion, c. 625C → T, in exon 3, resulting in a serine-to-proline change in codon 73 (S73P); a C → G transition, c. 751C → G, in exon 3, resulting in an arginine-to-glycine change in codon 115 (R115G); a T → C transversion of nucleotide 331 at 5’UTR in exon 2 (c.331 T → C); and a C → T transversion of the nucleotide 5 in intron 1 (IVS1 + 5C → T). The mutations were not present in the control group (n = 100).ConclusionsOur results extend the spectrum of NDP gene mutations. The mutations in the non-coding region of NDP may play a crucial role in the pathogenesis of FEVR.

Spectrum of gene mutations identified by targeted next-generation sequencing in Chinese leukemia patients.

BackgroundDespite targeted sequencing have identified several mutations for leukemia, there is still a limit of mutation screening for Chinese leukemia. Here, we used targeted next‐generation sequencing for testing the mutation patterns of Chinese leukemia patients.MethodsWe performed targeted sequencing of 504 tumor‐related genes in 109 leukemia samples to identify single‐nucleotide variants (SNVs) and insertions and deletions (INDELs). Pathogenic variants were assessed based on the American College of Medical Genetics and Genomics (ACMG) guidelines. The functional impact of pathogenic genes was explored through gene ontology (GO), pathway analysis, and protein–protein interaction network in silico.ResultsWe identified a total of 4,655 SNVs and 614 INDELs in 419 genes, in which PDE4DIP, NOTCH2, FANCA, BCR, and ROS1 emerged as the highly mutated genes. Of note, we were the first to demonstrate an association of PDE4DIP mutation and leukemia. Based on ACMG guidelines, 39 pathogenic and likely pathogenic mutations in 27 genes were found. GO annotation showed that the biological process including gland development, leukocyte differentiation, respiratory system development, myeloid leukocyte differentiation, mesenchymal to epithelial transition, and so on were involved.ConclusionOur study provided a map of gene mutations in Chinese patients with leukemia and gave insights into the molecular pathogenesis of leukemia.

HER2 and BRAF mutation in colorectal cancer patients: a retrospective study in Eastern China.

ObjectiveTo investigate the frequency and prognostic role of the human epidermal growth factor receptor 2 gene (HER2) and BRAF V600E gene mutation in Chinese patients with colorectal cancer (CRC).MethodsClinicopathological and survival information from 480 patients with stage I–III CRC were reviewed and recorded. HER2 amplification was analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), BRAF V600E mutation was tested by IHC and Sanger sequencing. The relationship between HER2 and BRAF V600E mutation status and clinicopathological characteristics and outcomes were determined.ResultsThe amplification of HER2 and BRAF V600E mutation were identified in 27 of 480 (5.63%) and 19 of 480 (3.96%) CRC patients, respectively. HER2 amplification significantly correlated with greater bowel wall invasion (P = 0.041) and more advanced TNM stage (I vs. II vs. III; 0 vs 5.78% vs. 7.41%, P = 0.013). Patients suffering from tumors with poor differentiation had a higher incidence rate of BRAF V600E mutation than those with moderate/well differentiation (7.77% vs 2.92%, P = 0.04). HER2 amplification was an independent prognostic factor for worse disease-free survival (DFS) (HR = 2.53, 95% CI: 1.21–5.30, P = 0.014).ConclusionThe prevalence of HER2 amplification and BRAF V600E mutation in stage I–III CRC patients in Chinese was 6% and 4%, respectively, and HER2 amplification appeared to be associated with a worse DFS. More comprehensive molecular classification and survival analysis are needed to validate our findings.

Screening Gene Mutations in Chinese Patients With Benign Essential Blepharospasm.

Objective: This study aimed to screen gene mutations in Chinese patients with benign essential blepharospasm (BEB) to understand its etiology.Methods: Twenty BEB patients diagnosed by clinical manifestations between April 2015 and October 2015 were enrolled. All the cases were investigated by questionnaires about general conditions, social behavioral factors, environmental factors, psychological factors, genetic factors, and previous diseases. In each patient, a total of 151 genes related to movement disorders were analyzed by second-generation sequencing.Results: Two patients had a family history of BEB, and they had SYNE1 and Cdkn1A-interacting zinc finger protein 1 (CIZ1) mutation, respectively. We found the SYNE1 mutation in seven patients, the CIZ1 mutation in two patients, the CACNA1A mutation in two patients, the LRRK2 mutation in two patients, and the FUS mutation in two patients. The C10orf2, TPP1, SLC1A3, PNKD, EIF4G1, SETX, PRRT2, SPTBN2, and TTBK2 mutations were found in only one patient, respectively, while not any mutation in the 151 genes were found in two patients. Some patients had mutations in two genes.Conclusion: Genetic factors, especially SYNE1 and CIZ1 mutations, contribute to the etiology of BEB.

Screening of PAH Common Mutations in Chinese Phenylketonuria Patients Using iPLEX MALDI-TOF MS.

Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (PAH) gene variants. Previous research has identified some PAH mutation hotspots in Chinese patients with PKU. In this study, we introduce a novel MassArray panel for screening the 29 common PAH gene mutations in Chinese patients using iPLEX MALDI-TOF MS. 105 Patients with PKU and known PAH gene mutations were genotyped using this MassArray panel. All of the 29 mutations screened were detected, and MassArray panel results were consistent with those obtained by Sanger sequencing. Fifty patients newly diagnosed with PKU were recruited in the double-blind experiment. PAH gene variants were detected in these 50 patients using the MassArray panel, and the results were verified with Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) methods. Our results show that the mutation detection rate using the MassArray panel with 29 mutations is 74% (95% CI, 65–83%), and the clinical genetic diagnosis rate is 54% (95% CI, 40–68%). This panel can be used as a high throughput, low cost, and rapid method for screening and diagnosing PAH gene mutations. The establishment of this approach provides proof-of-concept for future large-scale PAH mutation carrier screening in areas with high rates of PKU.

Genomic Profiling of Driver Gene Mutations in Chinese Patients With Non-Small Cell Lung Cancer.

Worldwide, especially in China, lung cancer accounts to a major cause of mortality related to cancer. Treatment decisions mainly depend on oncogenic driver mutations, which offer novel therapeutic targets for anticancer therapy. However, studies of genomic profiling of driver gene mutations in mainland China are rare. Hence, this is an extensive study of these mutations in Non-small-cell lung cancer (NSCLC) Chinese patients. Comparison of driver gene mutations of lung adenocarcinoma with other races showed that the mutational frequencies were similar within the different East Asian populations, while there were differences between East Asian and non-Asian populations. Further, four promising candidates for druggable mutations of epidermal growth factor receptor (EGFR) were revealed that open up avenues to develop and design personal therapeutic approaches for patients harboring mutations. These results will help to develop personalized therapy targeting NSCLC.

UMOD gene mutations in Chinese patients with autosomal dominant tubulointerstitial kidney disease: a pediatric case report and literature review

BackgroundAutosomal dominant tubulointerstitial kidney disease (ADTKD) caused by UMOD gene mutation (ADTKD-UMOD) is rare in children, characterized by hyperuricemia, gout, and progressive chronic kidney disease. It usually leads to end-stage renal failure at fiftieth decades. Here, we report a 3-year-old Chinese boy in an ADTKD family caused by a novel UMOD gene mutation.Case presentationA 3-year-old boy was admitted to our hospital because of persistent hematuria. Urinalysis showed BLD 2+ without proteinuria. The serum levels of uric acid, creatinine and electrolytes were normal. No renal cyst or calculus was found by ultrasonography. Renal biopsy was performed and focal and segmental glomerulosclerosis was found in 4 glomeruli among 35 glomeruli examined. His father was found with end-stage renal disease (ESRD) at the age of 29, and renal ultrasound showed several cysts in both kidneys. A novel heterozygous mutation (c.1648G > A,p.V550I) in exon 8 of UMOD gene was identified by whole exome sequencing in the family. SCBC Genome Browser alignment showed that V550 were highly conserved in uromodulin among different species. Software predicted that the mutation is suspected to be harmful. By literature review, there are 12 mutations of UMOD gene in 14 Chinese families including only one pediatric case(a 16-year-old girl).ConclusionsA novel heterozygous mutation (c.1648G > A,p.V550I) in exon 8 of UMOD gene was found in in a Chinese child case with ADTKD-UMOD, which extends our understanding of UMOD gene mutation spectrum and phenotype of ADTKD-UMOD in children.