Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients.


:The identification and interpretation of germline BRCA1/2 variants become increasingly important in breast and ovarian cancer (OC) treatment. However, there is no comprehensive analysis of the germline BRCA1/2 variants in a Chinese population. Here we performed a systematic review and meta-analysis on such variants from 94 publications. A total of 2,128 BRCA1/2 variant records were extracted, including 601 from BRCA1 and 632 from BRCA2. In addition, 414, 734, 449, and 307 variants were also recorded in the BIC, ClinVar, ENIGMA, and UMD databases, respectively, and 579 variants were newly reported. Subsequent analysis showed that the overall germline BRCA1/2 pathogenic variant frequency was 5.7% and 21.8% in Chinese breast and OC, respectively. Populations with high-risk factors exhibited a higher pathogenic variant percentage. Furthermore, the variant profile in Chinese is distinct from that in other ethnic groups with no distinct founder pathogenic variants. We also tested our in-house American College of Medical Genetics-guided pathogenicity interpretation procedure for Chinese BRCA1/2 variants. Our results achieved a consistency of 91.2-97.6% (5-grade classification) or 98.4-100% (2-grade classification) with public databases. In conclusion, this study represents the first comprehensive meta-analysis of Chinese BRCA1/2 variants and validates our in-house pathogenicity interpretation procedure, thereby providing guidance for further PARP inhibitor development and companion diagnostics in the Chinese population.


Hum Mutat


Human mutation


Gao X,Nan X,Liu Y,Liu R,Zang W,Shan G,Gai F,Zhang J,Li L,Cheng G,Song L




Has Abstract


2020-03-01 00:00:00












  • Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD.

    abstract::Primary ciliary dyskinesia (PCD) is an inherited disorder causing significant upper and lower respiratory tract morbidity and impaired fertility. Half of PCD patients show abnormal situs. Human disease loci have been identified but a mouse model without additional deleterious defects is elusive. The inversus viscerum ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lucas JS,Adam EC,Goggin PM,Jackson CL,Powles-Glover N,Patel SH,Humphreys J,Fray MD,Falconnet E,Blouin JL,Cheeseman MT,Bartoloni L,Norris DP,Lackie PM

    更新日期:2012-03-01 00:00:00

  • Pattern of connexin 26 (GJB2) mutations causing sensorineural hearing impairment in Ghana.

    abstract::Mutations of the connexin 26 gene (GJB2) were studied in 365 apparently unrelated individuals with profound nonsyndromic, sensorineural hearing impairment from Ghana, West Africa. Among 121 mutated chromosomes found, 110 carried the previously described R143W mutation. A total of 6 novel mutations: L79P, V178A, R184Q,...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hamelmann C,Amedofu GK,Albrecht K,Muntau B,Gelhaus A,Brobby GW,Horstmann RD

    更新日期:2001-01-01 00:00:00

  • BBS genotype-phenotype assessment of a multiethnic patient cohort calls for a revision of the disease definition.

    abstract::Bardet-Biedl syndrome (BBS) is a ciliopathy characterized by retinal degeneration, obesity, polydactyly, renal abnormalities, and cognitive impairment for which 15 causative genes have been identified. Here we present the results of a mutational analysis of our multiethnic cohort of 83 families (105 cases); 75.9% of t...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Deveault C,Billingsley G,Duncan JL,Bin J,Theal R,Vincent A,Fieggen KJ,Gerth C,Noordeh N,Traboulsi EI,Fishman GA,Chitayat D,Knueppel T,Millán JM,Munier FL,Kennedy D,Jacobson SG,Innes AM,Mitchell GA,Boycott K,Héon E

    更新日期:2011-06-01 00:00:00

  • D-glyceric aciduria is caused by genetic deficiency of D-glycerate kinase (GLYCTK).

    abstract::D-glyceric aciduria is a rare inborn error of serine and fructose metabolism that was first described in 1974. Most affected individuals have presented with neurological symptoms. The molecular basis of D-glyceric aciduria is largely unknown; possible causes that have been discussed are deficiencies of D-glycerate deh...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sass JO,Fischer K,Wang R,Christensen E,Scholl-Bürgi S,Chang R,Kapelari K,Walter M

    更新日期:2010-12-01 00:00:00

  • Two missense mutations causing mild hyperphenylalaninemia associated with DNA haplotype 12.

    abstract::The genetic defects responsible for most phenylketonuria (PKU) and hyperphenylalaninemia (HPA) cases are located in the phenylalanine hydroxylase (PAH) gene. Approximately 50-60 mutations have been reported in Caucasians and are reflected in a wide range of clinical severities. Most mutations are linked to specific ha...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Svensson E,Eisensmith RC,Dworniczak B,von Döbeln U,Hagenfeldt L,Horst J,Woo SL

    更新日期:1992-01-01 00:00:00

  • Two novel missense mutations of the OCTN2 gene (W283R and V446F) in a patient with primary systemic carnitine deficiency.

    abstract::Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder of fatty acid oxidation caused by defective cellular carnitine transport. The disease is characterized by metabolic derangement simulating Reye's syndrome, hypoglcaemia, progressive cardiomyopathy and skeletal myopathy. Recently, it was sho...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mayatepek E,Nezu J,Tamai I,Oku A,Katsura M,Shimane M,Tsuji A

    更新日期:2000-01-01 00:00:00

  • ADIPOR1 Is Mutated in Syndromic Retinitis Pigmentosa.

    abstract::Retinitis pigmentosa (RP) is a genetically heterogeneous retinal disorder. Despite the numerous genes associated with RP already identified, the genetic basis remains unknown in a substantial number of patients and families. In this study, we performed whole-exome sequencing to investigate the molecular basis of a syn...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Xu M,Eblimit A,Wang J,Li J,Wang F,Zhao L,Wang X,Xiao N,Li Y,Wong LJ,Lewis RA,Chen R

    更新日期:2016-03-01 00:00:00

  • Sedoheptulokinase deficiency due to a 57-kb deletion in cystinosis patients causes urinary accumulation of sedoheptulose: elucidation of the CARKL gene.

    abstract::The most common mutation in the nephropathic cystinosis (CTNS) gene is a homozygous 57-kb deletion that also includes an adjacent gene carbohydrate kinase-like (CARKL). The latter gene encodes a protein that is predicted to function as a carbohydrate kinase. Cystinosis patients with the common 57-kb deletion had stron...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wamelink MM,Struys EA,Jansen EE,Levtchenko EN,Zijlstra FS,Engelke U,Blom HJ,Jakobs C,Wevers RA

    更新日期:2008-04-01 00:00:00

  • Functional FEN1 polymorphisms are associated with DNA damage levels and lung cancer risk.

    abstract::Flap endonuclease 1 (FEN1) is a key enzyme in maintaining genomic stability and protecting against carcinogenesis. This study investigated whether functional variations in FEN1 gene are associated with DNA damage and lung cancer risk. Thirty DNA samples were sequenced to identify variants and function of the variants ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Yang M,Guo H,Wu C,He Y,Yu D,Zhou L,Wang F,Xu J,Tan W,Wang G,Shen B,Yuan J,Wu T,Lin D

    更新日期:2009-09-01 00:00:00

  • Characterization of 17 novel endoglin mutations associated with hereditary hemorrhagic telangiectasia.

    abstract::Hereditary hemorrhagic telangiectasia type 1 (HHT1) is a vascular dysplasia caused by mutations in the endoglin (ENG) gene and associated with epistaxis, telangiectases, and a high incidence of pulmonary arteriovenous malformations. To efficiently detect deletions and insertions, we optimized a quantitative multiplex ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cymerman U,Vera S,Karabegovic A,Abdalla S,Letarte M

    更新日期:2003-05-01 00:00:00

  • Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and classification of published variants in the ARSB gene.

    abstract::Maroteaux-Lamy syndrome (MPS VI) is an autosomal recessive lysosomal storage disorder caused by pathogenic ARSB gene variants, commonly diagnosed through clinical findings and deficiency of the arylsulfatase B (ASB) enzyme. Detection of ARSB pathogenic variants can independently confirm diagnosis and render genetic co...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Tomanin R,Karageorgos L,Zanetti A,Al-Sayed M,Bailey M,Miller N,Sakuraba H,Hopwood JJ

    更新日期:2018-12-01 00:00:00

  • Expanding the Molecular and Clinical Phenotype of SSR4-CDG.

    abstract::Congenital disorders of glycosylation (CDG) are a group of mostly autosomal recessive disorders primarily characterized by neurological abnormalities. Recently, we described a single CDG patient with a de novo mutation in the X-linked gene, Signal Sequence Receptor 4 (SSR4). We performed whole-exome sequencing to iden...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Ng BG,Raymond K,Kircher M,Buckingham KJ,Wood T,Shendure J,Nickerson DA,Bamshad MJ,University of Washington Center for Mendelian Genomics.,Wong JT,Monteiro FP,Graham BH,Jackson S,Sparkes R,Scheuerle AE,Cathey S,Kok F,Gib

    更新日期:2015-11-01 00:00:00

  • Fifth International Mutation Detection Workshop, May 13-16, 1999, Vicoforte, Italy.

    abstract::The Fifth International Mutation Detection Workshop brought together inventors and major users of mutation detection methodology in a freshly refurbished 17(th) century monastery in northern Italy. There were over 120 registrants from 22 nations, all of which gave either a poster or oral presentation, making it diffic...

    journal_title:Human mutation



    authors: Dianzani I,Landegren U,Camaschella C,Ponzone A,Piazza A,Cotton RG

    更新日期:1999-01-01 00:00:00

  • Sequence diversity of KIAA0027/MLC1: are megalencephalic leukoencephalopathy and schizophrenia allelic disorders?

    abstract::The aim of the study is to validate the etiological role of KIAA0027/MLC1 in childhood-onset megalencephalic leukoencephalopathy with subcortical cysts (MLC) and in schizophrenia, particularly the catatonic subtype, which were reported to be allelic diseases. Among a series of five patients with MLC, four mutant allel...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Rubie C,Lichtner P,Gärtner J,Siekiera M,Uziel G,Kohlmann B,Kohlschütter A,Meitinger T,Stöber G,Bettecken T

    更新日期:2003-01-01 00:00:00

  • Harmonized microarray/mutation scanning analysis of TP53 mutations in undissected colorectal tumors.

    abstract::Both the mutational status and the specific mutation of TP53 (p53) have been shown to impact both tumor prognosis and response to therapies. Molecular profiling of solid tumors is confounded by infiltrating wild-type cells, since normal DNA can interfere with detection of mutant sequences. Our objective was to identif...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Favis R,Huang J,Gerry NP,Culliford A,Paty P,Soussi T,Barany F

    更新日期:2004-07-01 00:00:00

  • Disease-causing mutations improving the branch site and polypyrimidine tract: pseudoexon activation of LINE-2 and antisense Alu lacking the poly(T)-tail.

    abstract::Cryptic exons or pseudoexons are typically activated by point mutations that create GT or AG dinucleotides of new 5' or 3' splice sites in introns, often in repetitive elements. Here we describe two cases of tetrahydrobiopterin deficiency caused by mutations improving the branch point sequence and polypyrimidine tract...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Meili D,Kralovicova J,Zagalak J,Bonafé L,Fiori L,Blau N,Thöny B,Vorechovsky I

    更新日期:2009-05-01 00:00:00

  • DMD genotype correlations from the Duchenne Registry: Endogenous exon skipping is a factor in prolonged ambulation for individuals with a defined mutation subtype.

    abstract::Antisense oligonucleotide (AON)-mediated exon skipping is an emerging therapeutic for individuals with Duchenne muscular dystrophy (DMD). Skipping of exons adjacent to common exon deletions in DMD using AONs can produce in-frame transcripts and functional protein. Targeted skipping of DMD exons 8, 44, 45, 50, 51, 52, ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wang RT,Barthelemy F,Martin AS,Douine ED,Eskin A,Lucas A,Lavigne J,Peay H,Khanlou N,Sweeney L,Cantor RM,Miceli MC,Nelson SF

    更新日期:2018-09-01 00:00:00

  • An NTD-associated polymorphism in the 3' UTR of MTHFD1L can affect disease risk by altering miRNA binding.

    abstract::Maternal folate levels and polymorphisms in folate-related genes are known risk factors for neural tube defects (NTDs). SNPs in the mitochondrial folate gene MTHFD1L are associated with the risk of NTDs. We investigated whether different alleles of SNP rs7646 in the 3' UTR of MTHFD1L can be differentially regulated by...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Minguzzi S,Selcuklu SD,Spillane C,Parle-McDermott A

    更新日期:2014-01-01 00:00:00

  • Detection of large gene rearrangements in X-linked genes by dosage analysis: identification of novel α-galactosidase A (GLA) deletions causing Fabry disease.

    abstract::For most Mendelian disorders, targeted genome sequencing is an effective method to detect causative mutations. However, sequencing PCR-amplified exonic regions and their intronic boundaries can miss large deletions or duplications and mutations that lead to PCR failures in autosomal dominant disorders and in heterozyg...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Dobrovolny R,Nazarenko I,Kim J,Doheny D,Desnick RJ

    更新日期:2011-06-01 00:00:00

  • DMD exon 1 truncating point mutations: amelioration of phenotype by alternative translation initiation in exon 6.

    abstract::Mutations in the DMD gene result in two common phenotypes associated with progressive muscle weakness: the more severe Duchenne muscular dystrophy (DMD) and the milder Becker muscular dystrophy (BMD). We have previously identified a nonsense mutation (c.9G>A; p.Trp3X) within the first exon of the DMD gene, encoding th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Gurvich OL,Maiti B,Weiss RB,Aggarwal G,Howard MT,Flanigan KM

    更新日期:2009-04-01 00:00:00

  • Mutations P51U and G122E in retinal transcription factor NRL associated with autosomal dominant and sporadic retinitis pigmentosa.

    abstract::Retinitis pigmentosa (RP) is the most frequent form of inherited retinopathy. RP is genetically heterogeneous with autosomal dominant, autosomal recessive and X-linked forms. Autosomal dominant retinitis pigmentosa (adRP) accounts for about 20-25% of all RP cases. At least ten adRP loci have so far been mapped. Howeve...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Martinez-Gimeno M,Maseras M,Baiget M,Beneito M,Antiñolo G,Ayuso C,Carballo M

    更新日期:2001-06-01 00:00:00

  • Molecular genetics of the long QT syndrome: two novel mutations of the KVLQT1 gene and phenotypic expression of the mutant gene in a large kindred.

    abstract::At least three different gene loci were recently shown to account for the long QT syndrome (LQTS), a monogenic disorder with altered myocardial repolarization and occurrence of life-threatening cardiac arrhythmias. We screened 44 unrelated probands for mutations of the gene encoding the cardiac potassium channel KVLQT...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Saarinen K,Swan H,Kainulainen K,Toivonen L,Viitasalo M,Kontula K

    更新日期:1998-01-01 00:00:00

  • Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

    abstract::Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APO...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: McKay GJ,Patterson CC,Chakravarthy U,Dasari S,Klaver CC,Vingerling JR,Ho L,de Jong PT,Fletcher AE,Young IS,Seland JH,Rahu M,Soubrane G,Tomazzoli L,Topouzis F,Vioque J,Hingorani AD,Sofat R,Dean M,Sawitzke J,Seddon

    更新日期:2011-12-01 00:00:00

  • High throughput detection of microsatellite instability by denaturing high-performance liquid chromatography.

    abstract::Microsatellite instability (MSI) is a hallmark of the DNA replication error phenotype, due to the inactivation of mismatch repair genes. MSI has been implicated in colon and many other gastrointestinal cancers. MSI usually can be analyzed by PCR amplification of microsatellite markers followed by electrophoresis and d...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pan KF,Liu W,Lu YY,Zhang L,Li ZP,Lu WL,Thibodeau SN,You WC

    更新日期:2003-11-01 00:00:00

  • Genomic variation in a global village: report of the 10th annual Human Genome Variation Meeting 2008.

    abstract::The Centre for Applied Genomics of the Hospital for Sick Children and the University of Toronto hosted the 10th Human Genome Variation (HGV) Meeting in Toronto, Canada, in October 2008, welcoming about 240 registrants from 34 countries. During the 3 days of plenary workshops, keynote address, and poster sessions, a st...

    journal_title:Human mutation



    authors: Brookes AJ,Chanock SJ,Hudson TJ,Peltonen L,Abecasis G,Kwok PY,Scherer SW

    更新日期:2009-07-01 00:00:00

  • Molecular Genetic Characterization of 151 Mut-Type Methylmalonic Aciduria Patients and Identification of 41 Novel Mutations in MUT.

    abstract::Isolated methylmalonic aciduria (MMA) is an autosomal-recessive disorder of propionate metabolism that is most commonly caused by mutations in the methylmalonyl-CoA mutase (MUT) gene (mut-type MMA). We investigated a cohort of 151 patients, classifying 114 patients as mut(0) and 32 as mut(-) (five not defined). As per...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Forny P,Schnellmann AS,Buerer C,Lutz S,Fowler B,Froese DS,Baumgartner MR

    更新日期:2016-08-01 00:00:00

  • Interpreting missense variants: comparing computational methods in human disease genes CDKN2A, MLH1, MSH2, MECP2, and tyrosinase (TYR).

    abstract::The human genome contains frequent single-basepair variants that may or may not cause genetic disease. To characterize benign vs. pathogenic missense variants, numerous computational algorithms have been developed based on comparative sequence and/or protein structure analysis. We compared computational methods that u...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chan PA,Duraisamy S,Miller PJ,Newell JA,McBride C,Bond JP,Raevaara T,Ollila S,Nyström M,Grimm AJ,Christodoulou J,Oetting WS,Greenblatt MS

    更新日期:2007-07-01 00:00:00

  • Next-generation genetic testing for retinitis pigmentosa.

    abstract::Molecular diagnostics for patients with retinitis pigmentosa (RP) has been hampered by extreme genetic and clinical heterogeneity, with 52 causative genes known to date. Here, we developed a comprehensive next-generation sequencing (NGS) approach for the clinical molecular diagnostics of RP. All known inherited retina...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Neveling K,Collin RW,Gilissen C,van Huet RA,Visser L,Kwint MP,Gijsen SJ,Zonneveld MN,Wieskamp N,de Ligt J,Siemiatkowska AM,Hoefsloot LH,Buckley MF,Kellner U,Branham KE,den Hollander AI,Hoischen A,Hoyng C,Klevering BJ

    更新日期:2012-06-01 00:00:00

  • A single mutation in the GALC gene is responsible for the majority of late onset Krabbe disease patients in the Catania (Sicily, Italy) region.

    abstract::A high proportion of patients with late onset forms of Krabbe disease is observed in a region north of Catania in Sicily. Molecular analysis in five families from this region shows that this condition is mainly due to a not previously described p.Gly41Ser substitution in the GALC gene that abolishes catalytic activity...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lissens W,Arena A,Seneca S,Rafi M,Sorge G,Liebaers I,Wenger D,Fiumara A

    更新日期:2007-07-01 00:00:00

  • In silico and in vivo models for Qatari-specific classical homocystinuria as basis for development of novel therapies.

    abstract::Homocystinuria is a rare inborn error of methionine metabolism caused by cystathionine β-synthase (CBS) deficiency. The prevalence of homocystinuria in Qatar is 1:1,800 births, mainly due to a founder Qatari missense mutation, c.1006C>T; p.R336C (p.Arg336Cys). We characterized the structure-function relationship of th...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Ismail HM,Krishnamoorthy N,Al-Dewik N,Zayed H,Mohamed NA,Giacomo VD,Gupta S,Häberle J,Thöny B,Blom HJ,Kruger WD,Ben-Omran T,Nasrallah GK

    更新日期:2019-02-01 00:00:00