Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature

AIM:To detect the pathogenic gene variant in a family with neurofibromatosis type 1(NF1).METHODS:This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology.After detecting the suspicious pathogenic variant type,the pathogenic variant sites of the patient and the patient’s family members were verified by multiple ligation dependent probe amplification and Sanger sequencing.Sift,polyphen-2,Mutation Taster and GERP++software were used to predict the pathogenicity of the unknown loci.The clinical data,diagnosis and treatment process of the patients were reviewed.Using the keyword“NF1;frameshift pathogenic variant”,relevant literature was gathered for analysis from Chinese and international databases,with articles dating from the establishment of each database to April 2022.RESULTS:A heterozygous frameshift pathogenic variant of NF1 in exon 33 was detected in the patient.The insertion of adenine in coding region 4486 resulted in the replacement of isoleucine with asparagine in protein 1497.Sanger sequencing validation and segregation analysis were performed,which demonstrated that the NF1 gene was cosegregated with the disease phenotype in this family.This study identified a novel NF1 heterozygous frameshift mutation c.4486dupA(p.I1497Nfs*12).Relevant literature retrieval found 7 Chinese articles and 12 foreign articles.With NF1 gene mutation,mutation types are diverse,including point mutation,frameshift mutation,splice site mutation,exon mutation,chimeric mutation and de novo mutation.Foreign reports are based on autosomal dominant inheritance.CONCLUSION:This study’s results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family,expanding the mutational spectrum of the NF1 gene.

A novel frameshift mutation in the beta-subunit of the epithelial sodium channel gene caused Liddle syndrome

Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmatory evidence of the diagnosis of Liddle syndrome.Methods DNA samples from the proband with early-onset,treatment-resistant hypertension and hypokalemia and 31 additional relatives were all sequenced for mutations in exon 13 of theβ-ENaC andγ-ENaC genes,using amplification by polymerase chain reaction and direct DNA sequencing.

Severe Wolfram Syndrome Caused by a Novel Frameshift Mutation in <i>WFS1</i>Gene: Effect on the WFS1/CaM Interaction and Phenotype-Genotype Correlation

Mutations in the WFS1 gene have been reported in Wolfram syndrome (WFS), a rare and autosomal recessive disorder defined by early onset of diabetes mellitus and progressive optic and hearing impairment. Only few data are available concerning the association between clinical and molecular aspects of the WFS. We present a consanguineous family with a patient presenting an early onset of WFS and severe manifestations. Sequencing of WFS1 gene was performed for all the family members to search for responsible mutation and bioinformatics tools were conducted to predict its effect on structure and function of the protein. We have detected a novel frameshift mutation in the proband at homozygous state and at the heterozygous state in the parents who have no WFS manifestations. In silico analysis predicted the pathogenicity of the mutation and could lead to a complete loss of its function. Thus, 3D modeling showed that the mutation abolishes the interaction of the CaM binding region to the N-terminal of WFS1 and then impairs the WFS1-CaM complex formation. Genotype-phenotype correlation study shows that the novel mutation predisposes to early onset of diabetes and severe symptoms observed in the proband. We also report the effect of the frameshift mutation on the CaM-WFS1 impaired binding, and we discuss its possible consequence in pancreatic β-cells dysfunction and its role in the early onset of diabetes. In conclusion, the combination of impaired functions of WFS1 including unproper interaction of the CaM, Ca2+ uptake, mitochondrial dysfunction, and apoptosis under the ER stress could be involved in the severe phenotype and early onset of WFS of our patient.

Carrimycin inhibits coronavirus replication by decreasing the efficiency of programmed–1 ribosomal frameshifting through directly binding to the RNA pseudoknot of viral frameshift-stimulatory element

The pandemic of SARS-CoV-2 worldwide with successive emerging variants urgently calls for small-molecule oral drugs with broad-spectrum antiviral activity.Here,we show that carrimycin,a new macrolide antibiotic in the clinic and an antiviral candidate for SARS-CoV-2 in phase III trials,decreases the efficiency of programmed–1 ribosomal frameshifting of coronaviruses and thus impedes viral replication in a broad-spectrum fashion.Carrimycin binds directly to the coronaviral frameshift-stimulatory element(FSE)RNA pseudoknot,interrupting the viral protein translation switch from ORF1a to ORF1b and thereby reducing the level of the core components of the viral replication and transcription complexes.Combined carrimycin with known viral replicase inhibitors yielded a synergistic inhibitory effect on coronaviruses.Because the FSE mechanism is essential in all coronaviruses,carrimycin could be a new broad-spectrum antiviral drug for human coronaviruses by directly targeting the conserved coronaviral FSE RNA.This finding may open a new direction in antiviral drug discovery for coronavirus variants.

假尿苷修饰体外转录mRNA在翻译过程中发生的+1核糖体框架移码

为应对世界范围内的COVID-19疫情,假尿苷(Ψ)修饰的体外转录mRNA(Ψ-IVT-mRNA)被授权应用于SARS-Cov-2 mRNA疫苗。最近,Ψ-IVT-mRNA被发现在翻译蛋白质时发生核糖体“滞顿”,导致+1核糖体移码,在体外和体内翻译出异常的蛋白质。在接种SARS-Cov-2 mRNA疫苗的人群,这种异常蛋白可能激发脱靶T细胞反应或抗体反应或产生其它意想不到的副作用。这一发现对研制有效“安全”的mRNA疫苗/药物有“警示”和指导意义。

常染色体隐性遗传性痉挛性共济失调一例并文献复习

目的探讨常染色体隐性遗传性痉挛性共济失调(autosomal recessive spastic ataxia of Charlevoix Saguenay,ARSACS)患者的临床、影像、病理及遗传学特点。方法选取2019年12月23日解放军总医院第六医学中心神经内科患者1例,回顾分析患者的临床、影像、腓肠神经活检病理及基因突变特点,并复习既往文献。结果本例患者男,21岁,2岁起病,首次发作表现为双下肢力弱及不耐受疲劳,11岁出现共济失调步态,17岁出现剪刀步态。主要临床表现为典型小脑共济失调、痉挛性截瘫和周围神经病“三联征”,头颅MRI示脑桥基底部和被盖部T2WI轴位横向条带状短T2信号,呈“4行2列”排列;脑桥小脑脚增粗,小脑上蚓部萎缩。神经电生理示运动神经潜伏期延长及波幅减低、传导速度减慢,感觉神经传导未检出确切波形。双侧胫骨前肌呈神经源性损害。腓肠神经活检病理示神经束内大、小有髓神经纤维密度中度减少,及散在分布的轴索变性及薄髓纤维。患者ARSACS基因存在p.D968Vfs*13和p.D1903Yfs*31的2处移码突变,分别来自患者父亲和母亲。既往文献未发现该突变报道,考虑为新发突变。结论ARSACS患者临床表现为典型“三联征”,头颅影像学表现为脑桥轴位T2WI呈“4行2列”排列的横向条带状短T2信号,腓肠神经活检呈慢性活动性轴索变性及髓鞘脱失,ARSACS基因新发突变。

Identification of a novel frameshift mutation in PITX2 gene in a Chinese family with Axenfeld-Rieger syndrome

Objective： Axenfeld-Rieger syndrome （ARS） is phenotypically and genetically heterogeneous. In this study we identified the underlying genetic defect in a Chinese family with ARS. Methods： A detailed family history and clinical data were recorded. The ocular phenotype was documented using slit-lamp photography and systemic anomalies were also documented where available. The genomic DNA was extracted from peripheral blood leukocytes. All coding exons and intron-exon junctions of paired-like homeodomain transcription factor 2 （PITX2） gene and the forkhead box C1 （FOXC1） gene were amplified by polymerase chain reaction （PCR） and screened for mutation by direct DNA sequencing. Variations detected in exon 5 of PITX2 were further evaluated with cloning sequencing. The exon 5 of PITX2 was also sequenced in 100 healthy controls, unrelated to the family, for comparison. Structural models of the wild type and mutant homeodomain of PITX2 were investigated by SWISS-MODEL. Results： Affected individuals exhibited variable ocular phenotypes, whereas the systemic anomalies were similar. After direct sequencing and cloning sequencing, a heterozygous deletion/insertion mutation c. 198_201delinsTTTCT （p.M661fs＊133） was revealed in exon 5 of PITX2. This mutation co-segregated with all affected individuals in the family and was not found either in unaffected family members or in 100 unrelated controls. Conclusions： We detected a novel frameshift mutation p.M661fs＊133 in PITX2 in a Chinese family with ARS. Although PITX2 mutations and polymorphisms have been re- ported from various ethnic groups, we report for the first time the identification of a novel deletion/insertion mutation that causes frameshift mutation in the homeodomain of PITX2 protein.

Novel Mutation of Cleidocranial Dysplasia-related Frameshift Runt-related Transcription Factor 2 in a Sporadic Chinese Case

Background： Cleidocranial dysplasia （CCD） is an autosomal dominant disease that affects the skeletal system. Common symptoms of CCD include hypoplasia or aplasia of the clavicles, delayed or even absent closure of the fontanels, midface hypoplasia, short stature, and delayed eruption of permanent and supernumerary teeth. Previous studies reported a connection between CCD and the haploinsufficiency of runt-related transcription factor 2 （RUNX2）. Here, we report a sporadic Chinese case presenting typical symptoms of CCD. Methods： We made genetic testing on this sporadic Chinese case and identified a novel RUNX2 ffameshift mutation： c.1111 dupT. In situ immunofluorescence microscopy and osteocalcin promoter luciferase assay were performed to compare the functions of the RUNX2 mutation with those of wild-type RUNX2. Results： RUNX2 mutation was observed in the perinuclear region, cytoplasm, and nuclei. In contrast, wild-type RUNX2 was confined in the nuclei, which indicated that the subcellular compartmentalization of RUNX2 mutation was partially perturbed. The transactivation function on osteocalcin promoter of the RUNX2 mutation was obviously abrogated. Conclusions： We identified a sporadic CCD patient carrying a novel insertion/frameshift mutation of RUNX2. This finding expanded our understanding of CCD-related phenotypes.

IRF8新发移码突变的基因功能分析

目的对反复肺炎患儿队列病因筛查中发现的干扰素调节因子8基因(interferon regulator factor 8,IRF8)新发突变(c.1266dupA)进行分子细胞水平的功能研究与验证。方法针对IRF8突变序列构建野生与突变蛋白过表达载体,通过质粒转染或构建慢病毒感染不同工具细胞,通过qPCR、Western blot、免疫荧光等实验手段检测其表达差异及对下游炎症相关基因表达调控的改变。结果IRF8野生及突变过表达载体构建成功,且转染效率可观,包装成的慢病毒感染效率亦较高。突变基因IRF8(c.1266dupA)相较于野生型IRF8转录水平降低,表达蛋白的相对分子质量略增大,表达量降低,突变蛋白IRF8mut相对野生型IRF8蛋白核质比增加,IRF8(c.1266dupA)对下游ISRE元件的抑制功能增强。结论IRF8新发移码突变属于功能获得型(gain of function,GOF)突变。

UPF1影响AU565乳腺癌细胞侵袭、迁移及EMT的机制

目的 探讨上游移码蛋白1(UPF1)对人乳腺癌细胞AU565侵袭、迁移及上皮间充质转化(EMT)的影响及机制研究。方法 收集2021年9月—2022年3月于我院接受乳腺切除术43例乳腺癌患者新鲜癌组织及正常乳腺组织,制备石蜡块,免疫组织化学法检测UPF1表达情况。购置人乳腺癌细胞系AU565及人乳腺上皮细胞系DU4475,激光共聚焦扫描显微镜法测定UPF1水平。采用小干扰RNA(siRNA)技术构建UPF1低表达的重组细胞,分析转染siRNA-UPF1对AU565细胞侵袭、迁移能力以及EMT相关蛋白表达和蛋白激酶B/哺乳动物雷帕霉素靶蛋白(Akt/mTOR)信号通路的影响。结果 乳腺癌组织UPF1的吸光度值显著高于正常乳腺组织(P<0.05)。AU565细胞UPF1荧光强度显著大于DU4475细胞(P<0.05)。与siRNA-NC组比较,转染siRNA-UPF1后AU565细胞中UPF1蛋白及mRNA表达水平均显著降低(P<0.05)。与siRNA-NC组比较,转染siRNA-UPF1后AU565细胞穿膜率和细胞迁移率均显著增加(P<0.05)。转染siRNA-UPF1后AU565细胞E-candherin蛋白表达水平显著降低,Vimentin和N-cadherin蛋白表达水平显著升高(P<0.05)。转染siRNA-UPF1后AU565细胞p-Akt和p-mTOR水平显著升高(P<0.05)。结论 UPF1在乳腺癌中表达上调,但沉默UPF1可能通过激活Akt/mTOR通路传导,促进乳腺癌细胞AU565的侵袭和迁移,并诱导EMT发生。

Identification of a novel mutation in the FGF10 gene in a Chinese family with obvious congenital lacrimal duct dysplasia in lacrimo-auriculo-dento-digital syndrome

AIM:To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome[LADD(MIM 149730)]showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene.METHODS:Ophthalmological examinations,including slit-lamp biomicroscopy and lacrimal duct probing,and computed tomography dacryocystography(CT-DCG)were performed for all participants.The family pedigree was drawn,genetic features were analyzed,and the genomic DNA of the subjects was extracted.Pathogenic genes were screened via whole exome sequencing(WES)and confirmed using Sanger sequencing.RESULTS:Six patients belonged to this three-generation family,and their clinical manifestations included congenital nasolacrimal duct obstruction,congenital absence of lacrimal puncta and canaliculi,lacrimal fistulae,and limb deformities.This pattern indicates autosomal dominant inheritance.Diagnosis was based on the clinical characteristics of LADD syndrome,which presented in all the patients in this family.A novel frameshif t mutation in the FGF10 gene(NM_004465.1),c.234dup C(p.Trp79Leus*15),was identified in all patients via WES.The variant was confirmed by Sanger sequencing and classified as a“pathogenic mutation”according to the American College of Medical Genetics and Genomics(ACMG)variant interpretation guidelines.CONCLUSION:A novel frameshift mutation in the FGF10 gene is found in all patients.This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene.

Novel mutation c.2090_2091del in neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities in an 18.5-mo-old boy:A case report

BACKGROUND Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities(NECRC)is a rare,autosomal,dominant neurological disorder caused by mutations in the ZMYM2 gene.To date,the clinical and functional characteristics of the novel ZMYM2 mutation c.2090_2091del have not yet been reported.CASE SUMMARY The patient was an 18.5-mo-old Chinese boy with motor and language delay,microcephaly,facial dysmorphism,moderate malnutrition,single palmar crease on the left hand,synpolydactyly of the right foot,hypotonia and feeding problems.The boy who was diagnosed with NECRC was enrolled in the First Affiliated Hospital,Henan University of Chinese Medicine,and his clinical data were collected.From the whole-exon sequencing(WES)data,the pathogenic SNVs/InDels were identified,and the molecular findings were characterized.WES revealed that the heterozygous variant in the ZMYM2 gene was c.2090_20-91del,p.Ser697TrpfsTer3,a frameshift mutation,which is a NECRC-related gene mutation.CONCLUSION We performed a systematic literature review to identify and characterize NECRC.Substantial evidence from the literature indicated that patients with ZMYM2 gene mutation showed different degrees of intellectual disability,motor and language retardation,facial dysmorphism,and a few had congenital heart defects,kidney and urinary tract abnormalities.Early diagnosis and prompt management with comprehensive rehabilitation training are beneficial,but may not improve long-term outcomes.

Rett综合征1例病例报道并文献复习

报道1例3月龄婴儿因小头畸形、生长发育迟缓行基因高通量测序,结果证实MECP2基因存在移码突变,结合临床表型确诊为Rett综合征的罕见男婴。患儿早期发育正常及发病年龄应大于6月龄不再视为确诊经典Rett综合征的必要条件。该病例报道将为低月龄Rett综合征的诊断提供一定参考,同时提高临床工作者对此病的认识,以期减少误诊及漏诊率。

卵泡蛋白基因的移码突变导致BHD综合征家系的多发性肺囊肿

目的Birt-Hogg-Dubé综合征(BHD)是一种常染色体显性遗传病,由卵泡蛋白(FLCN)基因突变引起,其特征以多发肺囊肿、皮肤纤维滤泡瘤和肾肿瘤为表现。方法我们对此家系进行了外显子组测序以确定先证者的致病基因变异,并进行了Sanger测序,以验证先证者和其家系成员的致病突变。同时采用Sanger测序验证了408例与该病无关的汉族健康对照组的突变。结果外显子组测序和Sanger测序分析显示在所有发病的家庭成员中,均存在移码突变(c.1579_1580invA,p.Arg527Glnfs68*)。蛋白印迹检测和免疫组化检测结果显示,该突变导致FLCN蛋白水平显著下降。结论FLCN基因(c.1579_1580invA,p.Arg527Glnfs68*)中的一个移码突变存在于一个仅以多个肺囊肿为表现的BHD综合征家系中;证实了该突变在BHD综合征家系中的致病性。

基于比较基因组学的解脂亚罗酵母CA20高产赤藓糖醇机理及进化分析

解脂亚罗酵母(Yarrowia lipolytica)是赤藓糖醇生产中使用的主要菌种,复合诱变是选育优良菌株的常用方法。然而,诱变处理所引起的基因组变化尚待探索。本研究对前期获得的高产菌株CA20和原始菌株WT5进行基因组测序,并与已发布的8株解脂亚罗酵母进行比较基因组分析,旨在探究菌株CA20高产赤藓糖醇的机理以及不同菌株的基因组进化关系。结果显示,菌株CA20基因组大小为20,420,510 bp,GC碱基含量为48.97%,编码6330个CDS和649个ncRNA,菌株CA20和其他8株菌高度同源,平均核苷酸同源性(average nucleotide identity,ANI)>99.50%,其中与菌株IBT 446和H222具有更近的亲缘关系。比较基因组分析显示,CA20和其他8株菌共有5342个核心基因,而CA20特有的65个基因主要参与物质跨膜运输和蛋白质转运过程。CA20基因组中含有166个碳水化合物活性酶(carbohydrate-active enzymes,CAZymes)基因,远多于其他菌株(108~137个),包括特有的4个糖苷水解酶类(glycoside hydrolases,GHs)、2个糖基转移酶类(glycosyltransferases,GTs)和13个碳水化合物酯酶类(carbohydrate esterases,CEs)。除转醛酶TAL1外,赤藓糖醇代谢途径有关酶在不同菌株中高度保守。此外,菌株CA20的赤藓糖醇产量和产率为190.97 g/L和1.33 g/L/h,显著高于WT5的128.61 g/L和0.92 g/L/h(P<0.001)。相比于WT5,CA20中5个基因发生移码变异,15个基因存在非同义突变位点,这些基因主要参与细胞分裂、细胞壁合成、蛋白质合成及稳态维持等过程。以上结果表明,解脂亚罗酵母基因组在进化过程中保守;生存环境不同是导致菌株间基因组差异的重要因素;基因组中CAZymes数量的差异是不同菌株间性能差异的原因之一;菌株CA20高产赤藓糖醇与其细胞结构及内环境稳定性的提升有关。本研究结果为赤藓糖醇高产菌株的定向选育提供基础。

成年起病-低钙血症-低PTH血症-TBX1移码缺失

甲状旁腺功能减退症(hypoparathyroidism, HP)是一种罕见的内分泌疾病,是由甲状旁腺激素(parathyroid hormone, PTH)合成或分泌缺乏引起的一组临床综合征,其临床特征包括低钙血症、高磷血症、神经肌肉兴奋性增高和软组织异位钙化。本文报道1例成年起病的HP患者,经基因检测发现TBX1移码缺失(NM_080647,exon3:c.161_186del/p.A54Afs*105),考虑诊断为DiGeorge综合征(DiGeorge syndrome, DGS)相关HP,提示临床医生对患者应进行仔细的体格检查和病史询问,有提示时,即使是成年起病的非手术性HP患者,也应考虑进行相关的基因筛查。

首次发现1例局灶性节段性肾小球硬化症患儿PAX2基因新的移码变异及文献复习

目的了解儿童遗传性慢性肾脏病的临床与病理特点,寻找其致病基因突变位点并分析基因突变与临床表型的关系,以期早期诊断,早期预防。方法收集徐州医科大学附属徐州儿童医院1例疑似为遗传性因素所致慢性肾脏病患儿及其直系亲属的临床资料,并行肾穿刺病理检查,同时采用二代基因测序方法对该患儿、患儿父母及妹妹进行基因检测,寻找可能的突变位点,并与该家系中正常个体进行比较。结果患儿为14岁男孩,3岁时起病,主要临床表现为蛋白尿、夜尿增多,未正规治疗。期间多次尿蛋白++~+++,且逐渐出现尿床症状,家长一直未予重视。2年前于当地医院查肝、肾功能,家长诉未见异常,2019年8月19日因尿床至我院就诊,门诊查尿蛋白+++,血尿素氮13.54 mmol/L,肌酐188μmol/L,肾脏超声提示双肾缩小,肾穿刺活检病理结果为局灶性节段性肾小球硬化症(FSGS)。基因检测示患儿PAX2基因存在c.143delGp.Gly48Valfs*35剪切位点突变,且目前尚未有人群携带记录,因而考虑该患儿为PAX2基因出现新的移码突变。结论该例患儿临床表现为慢性肾脏病,肾活检确诊为FSGS,基因检测PAX2基因发生新的移码变异。对于病因不明的慢性肾脏病患儿应注意完善肾脏病理及基因检测,有助于明确诊断。

Telomere erosion is independent of microsatellite instability but related to loss of heterozygosity in gastric cancer

AIM: To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas. METHODS: Telomeric restriction fragment (TRF) length of gastric cancer was measured with Southern blot. LOH of APC, MCC and DCC genes, microsatellite instability (MSI) and frameshift mutation of hMSH6, TGF-betaRII and BAX genes were analyzed by PCR-based methods. RESULTS: Sixty-eight cases of sporadic gastric carcinoma were studied for MSI using five microsatellite markers. MSI in at least one locus was detected in 17 (25%) of 68 tumors analyzed. Frameshift mutations of hMSH6, TGF-betaRII and BAX were detected in 2,6 and 3 of gastric carcinomas respectively showing high MSI (】 or = 2 loci, n = 8), but none was found in those showing low MSI (only one locus, n = 9) or MSS (tumor lacking MSI or stable, n = 51). Thirty-five cases, including all high MSI and low MSI, were studied for TRF. The mean TRF length was not correlated with clinicopathological parameters. No association was observed between TRF length and MSI or frameshift mutation. On the contrary, LOH at the DCC locus was related to telomere shortening (P【0.01). This tendency was also observed in APC and MCC genes, although there was no statistical significance. CONCLUSION: The development of gastric cancer can arise through two different genetic pathways. In high MSI gastric cancers, defective mismatch repair allows mutations to accumulate and generate the high MSI phenotype. In gastric cancers showing either low MSI or MSS, multiple deletions may represent the LOH pathway. Telomere erosion is independent of high MSI phenotype but related to the LOH pathway in gastric cancer.

A novel NF1 frame-shift mutation c.703＿704delTA in a Chinese pedigree with neurofibromatosis type 1

We analyzed the clinical features and NF1 gene mutation in a Chinese pedigree of neurofibromatosis type 1（NF1）. Three members of this family were NF1 patients presenting with different clinical phenotypes and the others were asymptomatic. Exons of NF1 were amplified by polymerase chain reaction, sequenced, compared with a reference database. One novel NF1 frame-shift mutation c.703_704delTA, which resulted in a premature stop signal at codon 720 and the synthesis of truncated, was revealed. This mutation segregated with the NF1 members is likely responsible for the pathogenesis of NF1 in the family.

中国一先天性无虹膜家系PAX6基因新致病突变位点的筛查及验证

背景先天性无虹膜是临床上罕见的先天性遗传性眼病。研究显示，配对盒转录因子6基因（PAX6）与先天性无虹膜症密切相关，但不同患者中PAX6基因的突变位点不同。目的对中国一常染色体显性遗传先天性无虹膜家系进行PAX6基因突变位点分析。方法于2014年8月在郑州大学第一附属医院收集一汉族先天性无虹膜家系，采集该家系9名成员及同期100名健康体检者的外周静脉血10ml，采用标准酚一氯仿提取法提取基因组DNA，对PCR扩增产物进行测序、对比及突变分析。采用实时荧光定量PCR法验证和比较该家系中患病者与该家系表型正常者和健康对照者淋巴细胞中PAX6mRNA的相对含量。结果该家系共3代9名成员，遗传方式符合常染色体显性遗传。家系中共5例患病者，成年患病者均表现为虹膜缺失和白内障，儿童患病者表现为无虹膜；其他4名家系成员表型正常。测序结果显示，家系患病者均存在11号染色体PAX6基因10号外显子的移码突变，第796位核糖核苷酸G缺失（C．796delG），产生提前终止密码子，而家系正常成员及100名对照者均无此突变。实时荧光定量PCR结果显示，家系中患病者淋巴细胞中PAX6mRNA表达水平比家系中正常成员约低50％，差异有统计学意义（Z=-2．449，P=0．016）。结论PAX6基因C．796delG为此先天性无虹膜家系的致病突变位点，扩增了PAX6基因突变谱。