GeneMatcher aids in the identification of a new malformation syndrome with intellectual disability, unique facial dysmorphisms, and skeletal and connective tissue abnormalities caused by de novo variants in HNRNPK.


:We report a new syndrome due to loss-of-function variants in the heterogeneous nuclear ribonucleoprotein K gene (HNRNPK). We describe two probands: one with a de novo frameshift (NM_002140.3: c.953+1dup), and the other with a de novo splice donor site variant (NM_002140.3: c.257G>A). Both probands have intellectual disability, a shared unique craniofacial phenotype, and connective tissue and skeletal abnormalities. The identification of this syndrome was made possible by a new online tool, GeneMatcher, which facilitates connections between clinicians and researchers based on shared interest in candidate genes. This report demonstrates that new Web-based approaches can be effective in helping investigators solve exome sequencing projects, and also highlights the newer paradigm of "reverse phenotyping," where characterization of syndromic features follows the identification of genetic variants.


Hum Mutat


Human mutation


Au PYB,You J,Caluseriu O,Schwartzentruber J,Majewski J,Bernier FP,Ferguson M,Care for Rare Canada Consortium.,Valle D,Parboosingh JS,Sobreira N,Innes AM,Kline AD




Has Abstract


2015-10-01 00:00:00












  • Identification of novel truncated androgen receptor (AR) mutants including unreported pre-mRNA splicing variants in the 22Rv1 hormone-refractory prostate cancer (PCa) cell line.

    abstract::Advanced prostate cancer (PCa) has emerged as a public health concern due to population aging. Although androgen deprivation has proven efficacy in this condition, most advanced PCa patients will have to face failure of androgen deprivation as a treatment. Mutations in the androgen receptor (AR) from tumor cells have ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Marcias G,Erdmann E,Lapouge G,Siebert C,Barthélémy P,Duclos B,Bergerat JP,Céraline J,Kurtz JE

    更新日期:2010-01-01 00:00:00

  • Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism.

    abstract::The beta-cell ATP-sensitive potassium channel is a key component of stimulus-secretion coupling in the pancreatic beta-cell. The channel couples metabolism to membrane electrical events, bringing about insulin secretion. Given the critical role of this channel in glucose homeostasis, it is not surprising that mutation...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Gloyn AL,Siddiqui J,Ellard S

    更新日期:2006-03-01 00:00:00

  • Elucidating the genetic architecture of Adams-Oliver syndrome in a large European cohort.

    abstract::Adams-Oliver syndrome (AOS) is a rare developmental disorder, characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Autosomal dominant forms of AOS are linked to mutations in ARHGAP31, DLL4, NOTCH1 or RBPJ, while DOCK6 and EOGT underlie autosomal recessive inheritance. Data ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Meester JAN,Sukalo M,Schröder KC,Schanze D,Baynam G,Borck G,Bramswig NC,Duman D,Gilbert-Dussardier B,Holder-Espinasse M,Itin P,Johnson DS,Joss S,Koillinen H,McKenzie F,Morton J,Nelle H,Reardon W,Roll C,Salih MA,Sa

    更新日期:2018-09-01 00:00:00

  • Molecular subtyping of gastric cancer combining genetic and epigenetic anomalies provides distinct clinicopathological features and prognostic impacts.

    abstract::Both genetic and epigenetic abnormalities play important roles in gastric cancer (GC) development. We investigated whether the molecular subtypes of gastric cancer by combining genetic and epigenetic anomalies define its clinicopathological features and prognosis. The CpG island methylator phenotype (CIMP), MLH1 methy...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Tahara T,Tahara S,Horiguchi N,Okubo M,Terada T,Yamada H,Yoshida D,Omori T,Osaki H,Maeda K,Kamano T,Funasaka K,Nagasaka M,Nakagawa Y,Shibata T,Ohmiya N

    更新日期:2019-03-01 00:00:00

  • Spectrum of GJB2 mutations in Turkey comprises both Caucasian and Oriental variants: roles of parental consanguinity and assortative mating.

    abstract::Considerable differences exist for the spectrum of GJB2 mutations in different populations. Screening for the c.35delG mutation in 256 independent probands, 154 multiplex (familial) and 102 simplex (sporadic), coming from different regions of Turkey revealed 37 (14.5%) homozygotes. The allele frequency of c.35delG ran...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Tekin M,Duman T,Boğoçlu G,Incesulu A,Comak E,Ilhan I,Akar N

    更新日期:2003-05-01 00:00:00

  • Two independent retrotransposon insertions at the same site within the coding region of BTK.

    abstract::Insertion of endogenous retrotransposon sequences accounts for approximately 0.2% of disease causing mutations. These insertions are mediated by the reverse transcriptase and endonuclease activity of long interspersed nucleotide (LINE-1) elements. The factors that control the target site selection in insertional mutag...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Conley ME,Partain JD,Norland SM,Shurtleff SA,Kazazian HH Jr

    更新日期:2005-03-01 00:00:00

  • A novel splice site mutation of the EXT2 gene in a Finnish hereditary multiple exostoses family. Mutations in brief no. 197. Online.

    abstract::Hereditary multiple exostoses is a dominantly inherited disease characterized by multiple benign osteochondromas. The affected individuals have an increased risk of developing sarcoma. A large Finnish family with hereditary multiple exostosis was analyzed to find the disease-causing mutation. Blood samples were obtain...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wolf M,Hemminki A,Kivioja A,Sistonen P,Kaitila I,Ervasti H,Kinnunen J,Karaharju E,Knuutila S

    更新日期:1998-01-01 00:00:00

  • Effects of a 9.6-kb deletion of the LDL receptor gene (FH Helsinki) on structure and levels of mRNA.

    abstract::FH Helsinki is a deletion of the low-density lipoprotein receptor (LDLR) gene that deletes 9.6 kb from intron 15 to exon 18. Screening for mutant transcripts by Northern blot analysis from a patient heterozygous for FH Helsinki revealed two mutant transcripts. One was a transcript where the proximal part of intron 15 ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Rødningen OK,Tonstad S,Ose L,Berg K,Leren TP

    更新日期:1998-01-01 00:00:00

  • Functional analysis of splicing mutations and of an exon 2 polymorphic variant of SERPING1/C1NH.

    abstract::Several sequence changes have been reported in hereditary angioedema patients in intron 2 of the SERPING1/C1NH gene, but their consequences on splicing have not been determined. We examined in cell transfection assays the consequences at the mRNA level of splicing mutations affecting either the +3 or the +5 donor site...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Duponchel C,Djenouhat K,Frémeaux-Bacchi V,Monnier N,Drouet C,Tosi M

    更新日期:2006-03-01 00:00:00

  • Functional characterization of splicing and ligand-binding domain variants in the LDL receptor.

    abstract::Familial hypercholesterolemia (FH) is an autosomal dominant disorder mostly caused by mutations in the LDLR gene. Although the detection of functional mutations in the LDLR gene provides an unequivocal diagnosis of the FH condition, there are many variants whose pathogenicity is still unknown. The aims of this study w...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Etxebarria A,Palacios L,Stef M,Tejedor D,Uribe KB,Oleaga A,Irigoyen L,Torres B,Ostolaza H,Martin C

    更新日期:2012-01-01 00:00:00

  • Diagnostic Exome Sequencing Identifies a Novel Gene, EMILIN1, Associated with Autosomal-Dominant Hereditary Connective Tissue Disease.

    abstract::Heritable connective tissue diseases are a highly heterogeneous family of over 200 disorders that affect the extracellular matrix. While the genetic basis of several disorders is established, the etiology has not been discovered for a large portion of patients, likely due to rare yet undiscovered disease genes. By per...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Capuano A,Bucciotti F,Farwell KD,Tippin Davis B,Mroske C,Hulick PJ,Weissman SM,Gao Q,Spessotto P,Colombatti A,Doliana R

    更新日期:2016-01-01 00:00:00

  • Hereditary fructose intolerance: functional study of two novel ALDOB natural variants and characterization of a partial gene deletion.

    abstract::Hereditary fructose intolerance (HFI) is an autosomal recessive metabolic disease caused by impaired functioning of human liver aldolase (ALDOB). At least 54 subtle/point mutations and only two large intragenic deletions have been found in the ALDOB gene. Here we report two novel ALDOB variants (p.R46W and p.Y343H) an...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Esposito G,Imperato MR,Ieno L,Sorvillo R,Benigno V,Parenti G,Parini R,Vitagliano L,Zagari A,Salvatore F

    更新日期:2010-12-01 00:00:00

  • mirVAFC: A Web Server for Prioritizations of Pathogenic Sequence Variants from Exome Sequencing Data via Classifications.

    abstract::Exome sequencing has been widely used to identify the genetic variants underlying human genetic disorders for clinical diagnoses, but the identification of pathogenic sequence variants among the huge amounts of benign ones is complicated and challenging. Here, we describe a new Web server named mirVAFC for pathogenic ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Li Z,Liu Z,Jiang Y,Chen D,Ran X,Sun ZS,Wu J

    更新日期:2017-01-01 00:00:00

  • Genetic findings in congenital bilateral aplasia of vas deferens patients and identification of six novel mutatations. Mutations in brief no. 138. Online.

    abstract::Congential bilateral aplasia of vas deferens (CBAVD), a form of male sterility, has been suggested to represent a "genital" form of cystic fibrosis (CF), as mutations in the CFTR gene have been identified in most patients with this condition. Interestingly, the 5T allele in intron 8 appeared to be the most frequent mu...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: de Meeus A,Guittard C,Desgeorges M,Carles S,Demaille J,Claustres M

    更新日期:1998-01-01 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

  • Heterozygous missense mutations in NFATC1 are associated with atrioventricular septal defect.

    abstract::Atrioventricular septal defect (AVSD) may occur as part of a complex disorder (e.g., Down syndrome, heterotaxy), or as isolate cardiac defect. Multiple lines of evidence support a role of calcineurin/NFAT signaling in AVSD, and mutations in CRELD1, a protein functioning as a regulator of calcineurin/NFAT signaling hav...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Ferese R,Bonetti M,Consoli F,Guida V,Sarkozy A,Lepri FR,Versacci P,Gambardella S,Calcagni G,Margiotti K,Piceci Sparascio F,Hozhabri H,Mazza T,Digilio MC,Dallapiccola B,Tartaglia M,Marino B,Hertog JD,De Luca A

    更新日期:2018-10-01 00:00:00

  • Cafe Variome: general-purpose software for making genotype-phenotype data discoverable in restricted or open access contexts.

    abstract::Biomedical data sharing is desirable, but problematic. Data "discovery" approaches-which establish the existence rather than the substance of data-precisely connect data owners with data seekers, and thereby promote data sharing. Cafe Variome ( was therefore designed to provide a general-pur...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lancaster O,Beck T,Atlan D,Swertz M,Thangavelu D,Veal C,Dalgleish R,Brookes AJ

    更新日期:2015-10-01 00:00:00

  • Retinitis pigmentosa mutations of SNRNP200 enhance cryptic splice-site recognition.

    abstract::Mutations in SNRP200 gene cause autosomal-dominant retinal disorder retinitis pigmentosa (RP). The protein product of SNRNP200 is BRR2, a DExD/H box RNA helicase crucial for pre-mRNA splicing. In this study, we prepared p.S1087L and p.R1090L mutations of human BRR2 using bacterial artificial chromosome recombineering ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cvačková Z,Matějů D,Staněk D

    更新日期:2014-03-01 00:00:00

  • Identification of three novel mutations in the USH1C gene and detection of thirty-one polymorphisms used for haplotype analysis.

    abstract::Usher syndrome (USH) is a clinically and genetically heterogeneous autosomal recessive disorder in which sensorineural hearing loss is associated with retinitis pigmentosa. Usher syndrome type 1, the most severe form, is characterized by profound congenital deafness, vestibular dysfunction, and prepubertal onset of re...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Zwaenepoel I,Verpy E,Blanchard S,Meins M,Apfelstedt-Sylla E,Gal A,Petit C

    更新日期:2001-01-01 00:00:00

  • Molecular heterogeneity of classical and Duarte galactosemia: mutation analysis by denaturing gradient gel electrophoresis.

    abstract::Classical galactosemia is caused by one common missense mutation (Q188R) and by several rare mutations in the galactose-1-phosphate uridyltransferase (GALT) gene. The most common variant of GALT, the Duarte variant, occurs as two types, Duarte-1 (D-1) and Duarte-2 (D-2), both of which carry the sequence change N314D. ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Greber-Platzer S,Guldberg P,Scheibenreiter S,Item C,Schuller E,Patel N,Strobl W

    更新日期:1997-01-01 00:00:00

  • MSeqDR mvTool: A mitochondrial DNA Web and API resource for comprehensive variant annotation, universal nomenclature collation, and reference genome conversion.

    abstract::Accurate mitochondrial DNA (mtDNA) variant annotation is essential for the clinical diagnosis of diverse human diseases. Substantial challenges to this process include the inconsistency in mtDNA nomenclatures, the existence of multiple reference genomes, and a lack of reference population frequency data. Clinicians ne...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Shen L,Attimonelli M,Bai R,Lott MT,Wallace DC,Falk MJ,Gai X

    更新日期:2018-06-01 00:00:00

  • Array-MLPA: comprehensive detection of deletions and duplications and its application to DMD patients.

    abstract::Multiplex ligation-dependent probe amplification (MLPA) is widely used to screen genes of interest for deletions and duplications. Since MLPA is usually based on size-separation of the amplification products, the maximum number of target sequences that can be screened in parallel is usually limited to approximately 40...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Zeng F,Ren ZR,Huang SZ,Kalf M,Mommersteeg M,Smit M,White S,Jin CL,Xu M,Zhou DW,Yan JB,Chen MJ,van Beuningen R,Huang SZ,den Dunnen J,Zeng YT,Wu Y

    更新日期:2008-01-01 00:00:00

  • Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy.

    abstract::Approximately two-thirds of Duchenne muscular dystrophy (DMD) patients show intragenic deletions ranging from one to several exons of the DMD gene and leading to a premature stop codon. Other deletions that maintain the translational reading frame of the gene result in the milder Becker muscular dystrophy (BMD) form o...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Béroud C,Tuffery-Giraud S,Matsuo M,Hamroun D,Humbertclaude V,Monnier N,Moizard MP,Voelckel MA,Calemard LM,Boisseau P,Blayau M,Philippe C,Cossée M,Pagès M,Rivier F,Danos O,Garcia L,Claustres M

    更新日期:2007-02-01 00:00:00

  • Annotation of functional impact of voltage-gated sodium channel mutations.

    abstract::Voltage-gated sodium channels are pore-forming transmembrane proteins that selectively allow sodium ions to flow across the plasma membrane according to the electro-chemical gradient thus mediating the rising phase of action potentials in excitable cells and playing key roles in physiological processes such as neurotr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hinard V,Britan A,Schaeffer M,Zahn-Zabal M,Thomet U,Rougier JS,Bairoch A,Abriel H,Gaudet P

    更新日期:2017-05-01 00:00:00

  • Dilated cardiomyopathy-associated BAG3 mutations impair Z-disc assembly and enhance sensitivity to apoptosis in cardiomyocytes.

    abstract::Dilated cardiomyopathy (DCM) is characterized by dilation of left ventricular cavity with systolic dysfunction. Clinical symptom of DCM is heart failure, often associated with cardiac sudden death. About 20-35% of DCM patients have apparent family histories and it has been revealed that mutations in genes for sarcomer...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Arimura T,Ishikawa T,Nunoda S,Kawai S,Kimura A

    更新日期:2011-12-01 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

  • 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

  • A fast polymerase chain reaction-mediated strategy for introducing repeat expansions into CAG-repeat containing genes.

    abstract::We describe a simple method for expanding CAG trinucleotides in CAG-repeat containing genes which, in contrast to other techniques, leaves the original gene sequence intact. Here, we expanded the CAG stretches of a plasmid clone containing the cDNA of the SCA3/MJD gene from 22 CAG up to > 130 CAG repeats using polymer...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Laccone F,Maiwald R,Bingemann S

    更新日期:1999-01-01 00:00:00

  • Novel mutations in the human sucrase-isomaltase gene (SI) that cause congenital carbohydrate malabsorption.

    abstract::Disaccharide intolerance I or congenital sucrase-isomaltase deficiency (CSID) is a disorder leading to maldigestion of disaccharides, which is autosomal recessively inherited. Here we analyzed the sucrase-isomaltase (SI) gene from 11 patients of Hungarian origin with congenital sucrase-isomaltase deficiency. Variants ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sander P,Alfalah M,Keiser M,Korponay-Szabo I,Kovács JB,Leeb T,Naim HY

    更新日期:2006-01-01 00:00:00

  • A diagnostic genetic test for the physical mapping of germline rearrangements in the susceptibility breast cancer genes BRCA1 and BRCA2.

    abstract::The BRCA1 and BRCA2 genes are involved in breast and ovarian cancer susceptibility. About 2 to 4% of breast cancer patients with positive family history, negative for point mutations, can be expected to carry large rearrangements in one of these two genes. We developed a novel diagnostic genetic test for the physical ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cheeseman K,Rouleau E,Vannier A,Thomas A,Briaux A,Lefol C,Walrafen P,Bensimon A,Lidereau R,Conseiller E,Ceppi M

    更新日期:2012-06-01 00:00:00