Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in which six ion-channel genes have been identified. The phenotype-genotype relationships of the HERG (human ether-a-go-go-related gene) mutati...Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in which six ion-channel genes have been identified. The phenotype-genotype relationships of the HERG (human ether-a-go-go-related gene) mutations are not fully understood. The objective of this study is to identify the underlying genetic basis of a Chinese family with LQTS and to characterize the clinical manifestations properties of the mutation. Single strand conformation polymorphism (SSCP) analyses were conducted on DNA fragments amplified by polymerase chain reaction from five LQT-related genes. Aberrant conformers were analyzed by DNA sequencing. A novel splice mutation in C-terminus of HERG was identified in this Chinese LQTS family,leading to the deletion of 11-bp at the acceptor splice site of Exon9 [Exon9 IVS del (-12→-2)]. The mutation might affect,through deficient splicing, the putative cyclic nucleotide binding domain (CNBD) of the HERG K+ channel. This mutation resulted in a mildly affected phenotype. Only the proband had a history of syncopes, while the other three individuals with long QT interval had no symptoms. Two other mutation carriers displayed normal phenotype. No sudden death occurred in the family. The 4 affected individuals and the two silent mutation carriers were all heterozygous for the mutation. It is the first splice mutation of HERG reported in Chinese LQTS families. Clinical data suggest that the CNBD mutation may be less malignant than mutations occurring in the pore region and be partially dominant over wild-type function.展开更多
Starch biosynthesis is a complex process that relies on the coordinated action of multiple enzymes.Resistant starch is not digested in the small intestine,thus preventing a rapid rise in the glycemic index.Starch synt...Starch biosynthesis is a complex process that relies on the coordinated action of multiple enzymes.Resistant starch is not digested in the small intestine,thus preventing a rapid rise in the glycemic index.Starch synthase 2a(SS2a)is a key enzyme in amylopectin biosynthesis that has significant effects on starch structure and properties.In this study,we identified an ss2a null mutant(M3-1413)with a single base mutation from an ethyl methane sulfonate(EMS)-mutagenized population of barley.The mutation was located at the 3'end of the first intron of the RNA splicing receptor(AG)site,and resulted in abnormal RNA splicing and two abnormal transcripts of ss2a,which caused the inactivation of the SS2a gene.The starch structure and properties were significantly altered in the mutant,with M3-1413 containing lower total starch and higher amylose and resistant starch levels.This study sheds light on the effect of barley ss2a null mutations on starch properties and will help to guide new applications of barley starch in the development of nutritious food products.展开更多
AIM： To identify the disease-causing mutation responsible for the presence of congenital cataract in a Chinese family. METHODS： The study recruited a four-generation Chinese pedigree affected by autosomal dominant c...AIM： To identify the disease-causing mutation responsible for the presence of congenital cataract in a Chinese family. METHODS： The study recruited a four-generation Chinese pedigree affected by autosomal dominant congenital cataract （ADCC）. Family history and the history of cataract extraction were recorded. Blood samples were collected from individuals for DNA extraction. Direct sequencing of congenital cataract-associated genes was performed. Single-strand conformational polymorphism and bioinformatic analysis were conducted to further study the mutation. RESULTS： Direct sequencing revealed a novel splice site mutation of c.30-2 A〉G in the CRYBA3/A1 gene. The mutation co-segregated within all affected individuals in the family and was not found in unaffected members or 100 unrelated normal controls. These results were further confirmed by single-strand conformational polymorphism and bioinformatic analysis using the Human Splicing Finder and MaxEnt online software and Annovar computer software. CONCLUSION： c,30-2 A〉G mutation of CRYBA3/A1 gene is a novel mutation and broadens the genetic spectrum of ADCC, KEYWORDS： splice site mutation; congenital cataract; CRYBA3/A1 gene展开更多
Interleukin 2 receptor gamma(IL2RG)is an important receptor component for interleukin-2(IL2)family cytokines including IL2,IL4,IL7,IL9,IL15,and IL21.1 IL2RG is located on the X-chromosome q13.1,encoding a common gamma...Interleukin 2 receptor gamma(IL2RG)is an important receptor component for interleukin-2(IL2)family cytokines including IL2,IL4,IL7,IL9,IL15,and IL21.1 IL2RG is located on the X-chromosome q13.1,encoding a common gamma chain(γC)that is essential in lymphoid development,especially in the modulation of T cell and natural killer(NK)cell immune responses.Mutations in the IL2RG gene cause X-linked severe combined immunodeficiency(X-SCID),which is a life-threatening rare disease.In typical X-SCID,the disease is characterized by a nearly complete absence of T cells and NK cells,alongside normal or elevated counts of non-functional B cells(T–B+NK−phenotype).Infants with X-SCID exhibit high susceptibility to bacterial and opportunistic infections.Here,we report a splice site mutation(c.924+5G>C)in the IL2RG gene in a 3-month-old boy presenting with a typical phenotype of X-SCID.展开更多
Duchenne muscular dystrophy(DMD)and Becker muscular dystrophy(BMD)are caused by mutations in the DMD gene.The aim of this study is to identify pathogenic DMD variants in probands and reduce the risk of recurrence of t...Duchenne muscular dystrophy(DMD)and Becker muscular dystrophy(BMD)are caused by mutations in the DMD gene.The aim of this study is to identify pathogenic DMD variants in probands and reduce the risk of recurrence of the disease in affected families.Variations in 100 unrelated DMD/BMD patients were detected by multiplex ligation-dependent probe amplification(MLPA)and next-generation sequencing(NGS).Pathogenic variants in DMD were successfully identified in all cases,and 11 of them were novel.The most common mutations were intragenic deletions(69%),with two hotspots located in the 5'end(exons 2–19)and the central of the DMD gene(exons 45–55),while point mutations were observed in 22%patients.Further,c.1149+1G>A and c.1150?2A>G were confirmed by hybrid minigene splicing assay(HMSA).This two splice site mutations would lead to two aberrant DMD isoforms which give rise to severely truncated protein.Therefore,the clinical use of MLPA,NGS,and HMSA is an effective strategy to identify variants.Importantly,eight embryos were terminated pregnancies according to prenatal diagnosis and a healthy boy was successfully delivered by preimplantation genetic diagnosis(PGD).Early and accurate genetic diagnosis is essential for prenatal diagnosis/PGD to reduce the risk of recurrence of DMD in affected families.展开更多
Objective： To establish a routine procedure for the detection of p53 mutations in hepatocellular carcinoma （HCC） surgical resections using the FASAY （functional analysis of separated alleles of p53 on yeast） proc...Objective： To establish a routine procedure for the detection of p53 mutations in hepatocellular carcinoma （HCC） surgical resections using the FASAY （functional analysis of separated alleles of p53 on yeast） procedure. Methods： p53 status was analyzed by FASAY and cDNA sequencing in 50 cases of HCC. After the extraction of RNA from the frozen tumor and corresponding normal tissues, reverse transcription RT-PCR was carried out using these samples. The assay can detect mutations of p53 mRNA between codons 67 and 347 by the DNA-binding activity of the protein and reveal them as red colonies. Results： Of the 50 specimens, 29 （58%） were positive （mutan0 by FASAY. Sequencing analysis confirmed that all 29 FASAY positive tumors harbored mutations, and that no mutations were detectable in any FASAY negative tumors. In 29 p53 mutations, 22 mutations were point missense mutation, 5 were deletions and 2 were splicing mutations. A novel splice mutation on splice donor of intron 6 was reported, which could produce two different mRNAs, respectively using the nearest upstream and downstream recessive splice donor sites. Conclusion： FASAY is a sensitive method for detecting the various types of p53 mutations in HCC, suggesting that the yeast functional assay for the detection of p53 mutations may be essential for elucidating their clinical significance.展开更多
AIM:To report a novel splicing mutation in the RPGR gene(encoding retinitis pigmentosa GTPase regulator)in a three-generation Chinese family with X-linked retinitis pigmentosa(XLRP).METHODS:Comprehensive ophthalmic ex...AIM:To report a novel splicing mutation in the RPGR gene(encoding retinitis pigmentosa GTPase regulator)in a three-generation Chinese family with X-linked retinitis pigmentosa(XLRP).METHODS:Comprehensive ophthalmic examinations including best corrected visual acuity,fundus photography,vision field,and pattern-visual evoked potential were performed to identify the disease phenotype of a six-yearold boy from the family(proband).Genomic DNA was extracted from peripheral blood of five available members of the pedigree.Whole-exome sequencing(WES),Sanger sequencing,and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR.Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants.RESULTS:The proband was diagnosed as having retinitis pigmentosa(RP).He had severe symptoms with early onset.A novel splicing mutation,c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing.Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped,leading to the subsequent deletion of 623 correct amino acids(c.529_619del p.Val177Glnfs*16).CONCLUSION:We identify a novel splice donor site mutation causing aberrant splicing of RPGR.Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.展开更多
TNNI3K(troponin-I interacting kinase)encodes a duo tyrosine and serine/threonine kinase implicated in cardiomyopathy,arrhythmias,and cardiac conduction disease(CCD).1 However,no direct downstream phosphorylation targe...TNNI3K(troponin-I interacting kinase)encodes a duo tyrosine and serine/threonine kinase implicated in cardiomyopathy,arrhythmias,and cardiac conduction disease(CCD).1 However,no direct downstream phosphorylation targets of TNNI3K have been identified yet.2 Here,we employed the CRISPR/Cas9 gene-editing technique to generate a splicing mutation in the 4th exon of zebrafish tnni3k ortholog gene that mimics a TNNI3K splicing variant identified from a patient family with cardiomyopathy and CCD.展开更多
Cystic fibrosis(CF)is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator(CFTR).To identify the potential pathogenic mutations in a Chinese patient with...Cystic fibrosis(CF)is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator(CFTR).To identify the potential pathogenic mutations in a Chinese patient with CF,we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions.The patient is a compound heterozygote of c.2909G>A,p.Gly970Asp in exon 18 and c.1210-3C>G in cis with a poly-T of 5T(T5)sequence,3 bp upstream in intron 9.The splicing effect of c.1210-3C>G was verified via minigene assay in vitro,indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript,whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10.Overall,c.1210-3C>G,the newly identified pathogenic mutation in our patient,in combination with T5 sequence in cis,affects the CFTR gene splicing and produces nearly no normal transcript in vitro.Moreover,this patient carries a p.Gly970Asp mutation,thus confirming the high-frequency of this mutation in Chinese patients with CF.展开更多
Neutral lipid storage disease with myopathy(NLSDM)is a rare autosomal recessive disorder,due to an enzymatic error of lipid metabolism.Patients present always with skeletal muscle myopathy and variable cardiac and hep...Neutral lipid storage disease with myopathy(NLSDM)is a rare autosomal recessive disorder,due to an enzymatic error of lipid metabolism.Patients present always with skeletal muscle myopathy and variable cardiac and hepatic involvement.NLSDM is caused by mutations in the PNPLA2 gene,which encodes the adipose triglyceride lipase(ATGL).Here we report the molecular characterization and clinical findings of two NLSDM siblings carrying the novel c.187t1G>C homozygous PNPLA2 mutation,localized in the splice site of intron 2.Molecular analyses revealed that neither aberrant PNPLA2 mRNA isoforms,nor ATGL mutated protein were detectable in patient’s cells.Clinically,both patients presented early onset muscle weakness,in particular of proximal upper limb muscles.In almost 15 years,muscle damage affected also distal upper limbs.This is a NLSDM family,displaying a severe PNPLA2 mutation in two siblings with clinical presentation characterized by an early onset,but a slowly evolution of severe myopathy.展开更多
基金Project (No. 021107613) supported by the Science and Technology Research Foundation of Zhejiang Province, China
文摘Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in which six ion-channel genes have been identified. The phenotype-genotype relationships of the HERG (human ether-a-go-go-related gene) mutations are not fully understood. The objective of this study is to identify the underlying genetic basis of a Chinese family with LQTS and to characterize the clinical manifestations properties of the mutation. Single strand conformation polymorphism (SSCP) analyses were conducted on DNA fragments amplified by polymerase chain reaction from five LQT-related genes. Aberrant conformers were analyzed by DNA sequencing. A novel splice mutation in C-terminus of HERG was identified in this Chinese LQTS family,leading to the deletion of 11-bp at the acceptor splice site of Exon9 [Exon9 IVS del (-12→-2)]. The mutation might affect,through deficient splicing, the putative cyclic nucleotide binding domain (CNBD) of the HERG K+ channel. This mutation resulted in a mildly affected phenotype. Only the proband had a history of syncopes, while the other three individuals with long QT interval had no symptoms. Two other mutation carriers displayed normal phenotype. No sudden death occurred in the family. The 4 affected individuals and the two silent mutation carriers were all heterozygous for the mutation. It is the first splice mutation of HERG reported in Chinese LQTS families. Clinical data suggest that the CNBD mutation may be less malignant than mutations occurring in the pore region and be partially dominant over wild-type function.
基金supported by the Major Program of National Agricultural Science and Technology of China(NK20220607)the Sichuan Science and Technology Program,China(2023YFH0041)。
文摘Starch biosynthesis is a complex process that relies on the coordinated action of multiple enzymes.Resistant starch is not digested in the small intestine,thus preventing a rapid rise in the glycemic index.Starch synthase 2a(SS2a)is a key enzyme in amylopectin biosynthesis that has significant effects on starch structure and properties.In this study,we identified an ss2a null mutant(M3-1413)with a single base mutation from an ethyl methane sulfonate(EMS)-mutagenized population of barley.The mutation was located at the 3'end of the first intron of the RNA splicing receptor(AG)site,and resulted in abnormal RNA splicing and two abnormal transcripts of ss2a,which caused the inactivation of the SS2a gene.The starch structure and properties were significantly altered in the mutant,with M3-1413 containing lower total starch and higher amylose and resistant starch levels.This study sheds light on the effect of barley ss2a null mutations on starch properties and will help to guide new applications of barley starch in the development of nutritious food products.
基金Supported by Key Program of National Natural Science Foundation of China(No.81130018)National NaturalScience Foundation of China(No.81371001+6 种基金No.81570822No.81428005No.81470612)Zhejiang Province Key Research and Development Program(No.2015C03042)Zhejiang Key Lab Fund of China(No.2011E10006)Zhejiang Provincial Natural Science Foundation of China(No.LY14H120002)Zhejiang Province Traditional Chinese medicine Fund project(No.2013ZA082)
文摘AIM： To identify the disease-causing mutation responsible for the presence of congenital cataract in a Chinese family. METHODS： The study recruited a four-generation Chinese pedigree affected by autosomal dominant congenital cataract （ADCC）. Family history and the history of cataract extraction were recorded. Blood samples were collected from individuals for DNA extraction. Direct sequencing of congenital cataract-associated genes was performed. Single-strand conformational polymorphism and bioinformatic analysis were conducted to further study the mutation. RESULTS： Direct sequencing revealed a novel splice site mutation of c.30-2 A〉G in the CRYBA3/A1 gene. The mutation co-segregated within all affected individuals in the family and was not found in unaffected members or 100 unrelated normal controls. These results were further confirmed by single-strand conformational polymorphism and bioinformatic analysis using the Human Splicing Finder and MaxEnt online software and Annovar computer software. CONCLUSION： c,30-2 A〉G mutation of CRYBA3/A1 gene is a novel mutation and broadens the genetic spectrum of ADCC, KEYWORDS： splice site mutation; congenital cataract; CRYBA3/A1 gene
基金supported by Shenzhen Science and Technology Program(Guangdong,China)(No.LCYX20220620105200001)Guangdong Basic and Applied Basic Research Foundation(Guangdong,China)(No.2024A1515011959)+2 种基金Shenzhen Medical Research Fund(Guangdong,China)(No.C2405002)Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(Guangdong,China)(No.SZGSP010)Shenzhen High-level Hospital Construction Fund(Guangdong,China)(No.G2022097).
文摘Interleukin 2 receptor gamma(IL2RG)is an important receptor component for interleukin-2(IL2)family cytokines including IL2,IL4,IL7,IL9,IL15,and IL21.1 IL2RG is located on the X-chromosome q13.1,encoding a common gamma chain(γC)that is essential in lymphoid development,especially in the modulation of T cell and natural killer(NK)cell immune responses.Mutations in the IL2RG gene cause X-linked severe combined immunodeficiency(X-SCID),which is a life-threatening rare disease.In typical X-SCID,the disease is characterized by a nearly complete absence of T cells and NK cells,alongside normal or elevated counts of non-functional B cells(T–B+NK−phenotype).Infants with X-SCID exhibit high susceptibility to bacterial and opportunistic infections.Here,we report a splice site mutation(c.924+5G>C)in the IL2RG gene in a 3-month-old boy presenting with a typical phenotype of X-SCID.
基金the National Key Research and Development Program of China(No.2016YFC1000703)the Medicine and Health Science and Technology Plan Projects in Zhejiang Province(No.2014KYA246)the National Natural Science Foundation of China(Nos.81801441 and 81300532)
文摘Duchenne muscular dystrophy(DMD)and Becker muscular dystrophy(BMD)are caused by mutations in the DMD gene.The aim of this study is to identify pathogenic DMD variants in probands and reduce the risk of recurrence of the disease in affected families.Variations in 100 unrelated DMD/BMD patients were detected by multiplex ligation-dependent probe amplification(MLPA)and next-generation sequencing(NGS).Pathogenic variants in DMD were successfully identified in all cases,and 11 of them were novel.The most common mutations were intragenic deletions(69%),with two hotspots located in the 5'end(exons 2–19)and the central of the DMD gene(exons 45–55),while point mutations were observed in 22%patients.Further,c.1149+1G>A and c.1150?2A>G were confirmed by hybrid minigene splicing assay(HMSA).This two splice site mutations would lead to two aberrant DMD isoforms which give rise to severely truncated protein.Therefore,the clinical use of MLPA,NGS,and HMSA is an effective strategy to identify variants.Importantly,eight embryos were terminated pregnancies according to prenatal diagnosis and a healthy boy was successfully delivered by preimplantation genetic diagnosis(PGD).Early and accurate genetic diagnosis is essential for prenatal diagnosis/PGD to reduce the risk of recurrence of DMD in affected families.
基金Project (No. 39980020) supported by the National Natural Science Foundation of China
文摘Objective： To establish a routine procedure for the detection of p53 mutations in hepatocellular carcinoma （HCC） surgical resections using the FASAY （functional analysis of separated alleles of p53 on yeast） procedure. Methods： p53 status was analyzed by FASAY and cDNA sequencing in 50 cases of HCC. After the extraction of RNA from the frozen tumor and corresponding normal tissues, reverse transcription RT-PCR was carried out using these samples. The assay can detect mutations of p53 mRNA between codons 67 and 347 by the DNA-binding activity of the protein and reveal them as red colonies. Results： Of the 50 specimens, 29 （58%） were positive （mutan0 by FASAY. Sequencing analysis confirmed that all 29 FASAY positive tumors harbored mutations, and that no mutations were detectable in any FASAY negative tumors. In 29 p53 mutations, 22 mutations were point missense mutation, 5 were deletions and 2 were splicing mutations. A novel splice mutation on splice donor of intron 6 was reported, which could produce two different mRNAs, respectively using the nearest upstream and downstream recessive splice donor sites. Conclusion： FASAY is a sensitive method for detecting the various types of p53 mutations in HCC, suggesting that the yeast functional assay for the detection of p53 mutations may be essential for elucidating their clinical significance.
基金Supported by National Natural Science Foundation of China(No.31751003)Natural Science Foundation of Zhejiang Province(No.LY20H120009)+1 种基金Health Commission of Zhejiang Province(No.2022KY168)Beijing Bethune Charitable Foundation(No.BJ-GY2021013J).
文摘AIM:To report a novel splicing mutation in the RPGR gene(encoding retinitis pigmentosa GTPase regulator)in a three-generation Chinese family with X-linked retinitis pigmentosa(XLRP).METHODS:Comprehensive ophthalmic examinations including best corrected visual acuity,fundus photography,vision field,and pattern-visual evoked potential were performed to identify the disease phenotype of a six-yearold boy from the family(proband).Genomic DNA was extracted from peripheral blood of five available members of the pedigree.Whole-exome sequencing(WES),Sanger sequencing,and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR.Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants.RESULTS:The proband was diagnosed as having retinitis pigmentosa(RP).He had severe symptoms with early onset.A novel splicing mutation,c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing.Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped,leading to the subsequent deletion of 623 correct amino acids(c.529_619del p.Val177Glnfs*16).CONCLUSION:We identify a novel splice donor site mutation causing aberrant splicing of RPGR.Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.
基金supported in part by the National Natural Science Foundation of China(No.31970504,31772548,82371863,82070394)the NHC Key Laboratory of Birth Defect for Research and Prevention(Hunan Provincial Maternal and Child Health Care Hospital)(No.KF2021003)the Postgraduate Scientific Innovation Fund of Hunan Province,China(No.CX2018B302).
文摘TNNI3K(troponin-I interacting kinase)encodes a duo tyrosine and serine/threonine kinase implicated in cardiomyopathy,arrhythmias,and cardiac conduction disease(CCD).1 However,no direct downstream phosphorylation targets of TNNI3K have been identified yet.2 Here,we employed the CRISPR/Cas9 gene-editing technique to generate a splicing mutation in the 4th exon of zebrafish tnni3k ortholog gene that mimics a TNNI3K splicing variant identified from a patient family with cardiomyopathy and CCD.
基金supported by the National Key Research and Development Program of China(No.2016YFC0901502 to Kai-Feng Xu,No.2016YFC0905100 to Xue Zhang,No.2017YFC1001201 to Yaping Liu)the National Natural Science Foundation of China(NSFC)(Nos.81788101,81230015 to Xue Zhang,No.31271345 to Yaping Liu)+1 种基金the CAMS Initiative for Medical Sciences(CIFMS)(No.2016-I2M-1-002 to Xue Zhang,Yaping LiuNo.2018-I2M-1-003 to Xinlun Tian,No.2017-I2M-2-001 to Kai-Feng Xu).
文摘Cystic fibrosis(CF)is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator(CFTR).To identify the potential pathogenic mutations in a Chinese patient with CF,we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions.The patient is a compound heterozygote of c.2909G>A,p.Gly970Asp in exon 18 and c.1210-3C>G in cis with a poly-T of 5T(T5)sequence,3 bp upstream in intron 9.The splicing effect of c.1210-3C>G was verified via minigene assay in vitro,indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript,whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10.Overall,c.1210-3C>G,the newly identified pathogenic mutation in our patient,in combination with T5 sequence in cis,affects the CFTR gene splicing and produces nearly no normal transcript in vitro.Moreover,this patient carries a p.Gly970Asp mutation,thus confirming the high-frequency of this mutation in Chinese patients with CF.
基金grant GGP14066 from Telethon Foundationthe patient for their kind cooperation,to the EuroBioBank and the Telethon Network of Genetic Biobanks(GTB12001F)for providing biological samples and to professor Francesco Mauri for his scientific assistance。
文摘Neutral lipid storage disease with myopathy(NLSDM)is a rare autosomal recessive disorder,due to an enzymatic error of lipid metabolism.Patients present always with skeletal muscle myopathy and variable cardiac and hepatic involvement.NLSDM is caused by mutations in the PNPLA2 gene,which encodes the adipose triglyceride lipase(ATGL).Here we report the molecular characterization and clinical findings of two NLSDM siblings carrying the novel c.187t1G>C homozygous PNPLA2 mutation,localized in the splice site of intron 2.Molecular analyses revealed that neither aberrant PNPLA2 mRNA isoforms,nor ATGL mutated protein were detectable in patient’s cells.Clinically,both patients presented early onset muscle weakness,in particular of proximal upper limb muscles.In almost 15 years,muscle damage affected also distal upper limbs.This is a NLSDM family,displaying a severe PNPLA2 mutation in two siblings with clinical presentation characterized by an early onset,but a slowly evolution of severe myopathy.
