Lake Louise mutation detection meeting 2013: clinical translation of next-generation sequencing requires optimization of workflows and interpretation of variants.


:With the exponential reduction of the cost of next-generation sequencing (NGS), it is no longer the generation of data but the analysis and interpretation of massive amounts of sequencing data that are seen as key challenges for the effective integration of these technologies into clinical practice. Clinical geneticists, informaticians, and scientists from 17 countries gathered for the 12th International Symposium on Mutation in the Genome at the Fairmont Chateau Lake Louise (Canada) to discuss technological advances and applications of NGS and consider possible approaches to the challenges of clinical translation. Here, we provide an overview of the main themes of the meeting that included development of innovative solutions for variant sharing, tools and resources for NGS analysis, novel technology and methodology development, NGS-based discovery of disease pathogenesis, development of multigene NGS sequencing panels for clinical use, exploring diagnostic utility of whole-exome and whole-genome sequencing, and, finally, integration of genomic sequencing into the clinic.


Hum Mutat


Human mutation


Smith A,Boycott KM,Jarinova O




Has Abstract


2014-02-01 00:00:00












  • Novel TSC2 mutations and decreased expression of tuberin in cultured tumor cells with an insertion mutation.

    abstract::Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by hamartomas in many organs. Two genes responsible for TSC, TSC1 and TSC2, were recently identified. TSC1 and TSC2 encode the proteins hamartin and tuberin, respectively, and 337 different mutations have been reported in these genes thus...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Feng JH,Yamamoto T,Nanba E,Ninomiya H,Oka A,Ohno K

    更新日期:2004-04-01 00:00:00

  • Microsatellite in the 3' untranslated region of human fibroblast growth factor 9 (FGF9) gene exhibits pleiotropic effect on modulating FGF9 protein expression.

    abstract::Fibroblast growth factor 9 (FGF9) is a member of secreted polypeptide families and involved in many important biological processes, including implantation and morphogenesis during embryogenesis and adult life. Recently, Fgf9-knockout mice exhibited male-to-female sex reversal, demonstrating a novel function for FGF9 i...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chen TM,Kuo PL,Hsu CH,Tsai SJ,Chen MJ,Lin CW,Sun HS

    更新日期:2007-01-01 00:00:00

  • Exploring the use of molecular dynamics in assessing protein variants for phenotypic alterations.

    abstract::With the advent of rapid sequencing technologies, making sense of all the genomic variations that we see among us has been a major challenge. A plethora of algorithms and methods exist that try to address genome interpretation through genotype-phenotype linkage analysis or evaluating the loss of function/stability mut...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Garg A,Pal D

    更新日期:2019-09-01 00:00:00

  • Chemical chaperone therapy: chaperone effect on mutant enzyme and cellular pathophysiology in β-galactosidase deficiency.

    abstract::β-Galactosidase deficiency is a group of lysosomal lipid storage disorders with an autosomal recessive trait. It causes two clinically different diseases, G(M1) -gangliosidosis and Morquio B disease. It is caused by heterogeneous mutations in the GLB1 gene coding for the lysosomal acid β-galactosidase. We have previou...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Higaki K,Li L,Bahrudin U,Okuzawa S,Takamuram A,Yamamoto K,Adachi K,Paraguison RC,Takai T,Ikehata H,Tominaga L,Hisatome I,Iida M,Ogawa S,Matsuda J,Ninomiya H,Sakakibara Y,Ohno K,Suzuki Y,Nanba E

    更新日期:2011-07-01 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

  • Natural haplotypes in the regulatory sequences affect human alcohol dehydrogenase 1C (ADH1C) gene expression.

    abstract::Human alcohol dehydrogenases (ADHs) play important roles in metabolizing alcohol, and several lines of evidence suggest that variations in ADH genes affect the risk for alcoholism. Differences in regulatory sequences could affect the expression of ADH genes and thereby modify the risk for alcoholism. To explore this i...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chen HJ,Tian H,Edenberg HJ

    更新日期:2005-02-01 00:00:00

  • A novel nonstop mutation in TYMP does not induce nonstop mRNA decay in a MNGIE patient with severe neuropathy.

    abstract::The cellular quality control systems enable surveillance and selective degradation of nonsense, nonstop, and no-go mRNAs. In the case of nonstop mRNA, different mechanisms of nonstop-mediated decay (NSD) have been described for bacteria, yeast and mammals, but the molecular consequences of nonstop mutations have been ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Torres-Torronteras J,Rodriguez-Palmero A,Pinós T,Accarino A,Andreu AL,Pintos-Morell G,Martíí R

    更新日期:2011-04-01 00:00:00

  • Detection of heterozygous deletions and duplications in the MECP2 gene in Rett syndrome by Robust Dosage PCR (RD-PCR).

    abstract::Fifty to eighty percent of Rett syndrome (RTT) cases have point mutations in the gene encoding methyl-CpG-binding protein-2 (MECP2). A fraction of MECP2 negative classical RTT patients has large heterozygous deletions. Robust Dosage PCR (RD-PCR) assays were developed as a rapid, convenient and accurate method to detec...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Shi J,Shibayama A,Liu Q,Nguyen VQ,Feng J,Santos M,Temudo T,Maciel P,Sommer SS

    更新日期:2005-05-01 00:00:00

  • Truncating somatic mutation in exon 15 of the APC gene is a rare event in human breast carcinomas. Mutations in brief no. 179. Online.

    abstract::Inactivation of the adenomatous polyposis coli (APC) gene is an early event in sporadic colorectal cancer. Somatic mutations have also been detected in cancers of the stomach, pancreas, thyroid, ovary and breast. Over 95% of the mutations reported in the APC gene are frameshift and nonsense mutations. The large exon 1...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Sørlie T,Bukholm I,Børresen-Dale AL

    更新日期:1998-01-01 00:00:00

  • A large deletion mutation in the CFTR gene (3120+1Kbdel8.6Kb): a founder mutation in the Palestinian Arabs. Mutation in brief no. 231. Online.

    abstract::A deletion mutation of 8.6Kb in the CFTR gene, spanning the exons 17a, 17b and 18 was identified in 4 homozygous unrelated Palestinian CF patients. The patients were of various ethnic subgroups including Muslims, Christians and Druze. The deletion breakpoint occurred within an identical 4bp sequence in introns 16 and ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lerer I,Laufer-Cahana A,Rivlin JR,Augarten A,Abeliovich D

    更新日期:1999-01-01 00:00:00

  • Characterization of eleven novel mutations (M45L, R119H, 544delG, G145V, H154Y, C184Y, D289V, 862+5A, 1172delC, R411X, E459K) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with severe hypophosphatasia. Mutations in brief no. 217

    abstract::Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/ bone/kidney tissue alkaline phosphatase (L/B/K ALP) activity. We report the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 9 familie...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Taillandier A,Zurutuza L,Muller F,Simon-Bouy B,Serre JL,Bird L,Brenner R,Boute O,Cousin J,Gaillard D,Heidemann PH,Steinmann B,Wallot M,Mornet E

    更新日期:1999-01-01 00:00:00

  • A Novel KCNJ13 Nonsense Mutation and Loss of Kir7.1 Channel Function Causes Leber Congenital Amaurosis (LCA16).

    abstract::Mutations in the KCNJ13 gene that encodes the inwardly rectifying potassium channel Kir7.1 cause snowflake vitreoretinal degeneration (SVD) and leber congenital amaurosis (LCA). Kir7.1 controls the microenvironment between the photoreceptors and the retinal pigment epithelium (RPE) and also contributes to the function...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pattnaik BR,Shahi PK,Marino MJ,Liu X,York N,Brar S,Chiang J,Pillers DA,Traboulsi EI

    更新日期:2015-07-01 00:00:00

  • Cytogenetically visible inversions are formed by multiple molecular mechanisms.

    abstract::Cytogenetically detected inversions are generally assumed to be copy number and phenotypically neutral events. While nonallelic homologous recombination is thought to play a major role, recent data suggest the involvement of other molecular mechanisms in inversion formation. Using a combination of short-read whole-gen...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pettersson M,Grochowski CM,Wincent J,Eisfeldt J,Breman AM,Cheung SW,Krepischi ACV,Rosenberg C,Lupski JR,Ottosson J,Lovmar L,Gacic J,Lundberg ES,Nilsson D,Carvalho CMB,Lindstrand A

    更新日期:2020-11-01 00:00:00

  • The intellectual disability-associated CAMK2G p.Arg292Pro mutation acts as a pathogenic gain-of-function.

    abstract::The abundantly expressed calcium/calmodulin-dependent protein kinase II (CAMK2), alpha (CAMK2A), and beta (CAMK2B) isoforms are essential for learning and memory formation. Recently, a de novo candidate mutation (p.Arg292Pro) in the gamma isoform of CAMK2 (CAMK2G) was identified in a patient with severe intellectual d...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Proietti Onori M,Koopal B,Everman DB,Worthington JD,Jones JR,Ploeg MA,Mientjes E,van Bon BW,Kleefstra T,Schulman H,Kushner SA,Küry S,Elgersma Y,van Woerden GM

    更新日期:2018-12-01 00:00:00

  • Three Novel Heterozygous Point Mutations of NR3C1 Causing Glucocorticoid Resistance.

    abstract::Generalized glucocorticoid resistance is associated with glucocorticoid receptor (GR; NR3C1) mutations. Three novel heterozygous missense NR3C1 mutations (R477S, Y478C, and L672P) were identified in patients presenting with adrenal incidentalomas, glucocorticoid excess without Cushing syndrome. Dexamethasone (DXM) bin...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Vitellius G,Fagart J,Delemer B,Amazit L,Ramos N,Bouligand J,Le Billan F,Castinetti F,Guiochon-Mantel A,Trabado S,Lombès M

    更新日期:2016-08-01 00:00:00

  • Detection of more than 94% cystic fibrosis mutations in a sample of Belgian population and identification of four novel mutations.

    abstract::We have analysed 194 Belgian CF chromosomes using a variety of techniques: delta F508 was detected by polyacrylamide gel electrophoresis; dot blotting of PCR products was used to identify the mutations G542X, 1717-1 G-->A, and N1303K; molecular defects in exons 2, 3, 4, 5, 6b, 7, 11, 12, 13, 14a, 14b, 17b, 19, 20, and...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mercier B,Lissens W,Audrézet MP,Bonduelle M,Liebaers I,Ferec C

    更新日期:1993-01-01 00:00:00

  • CAGI 5 splicing challenge: Improved exon skipping and intron retention predictions with MMSplice.

    abstract::Pathogenic genetic variants often primarily affect splicing. However, it remains difficult to quantitatively predict whether and how genetic variants affect splicing. In 2018, the fifth edition of the Critical Assessment of Genome Interpretation proposed two splicing prediction challenges based on experimental perturb...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cheng J,Çelik MH,Nguyen TYD,Avsec Ž,Gagneur J

    更新日期:2019-09-01 00:00:00

  • New alleles at microsatellite loci in CEPH families mainly arise from somatic mutations in the lymphoblastoid cell lines.

    abstract::In the analysis of 40 CEPH families, under the EUROGEM project, with a total of 29 microsatellites (26 CA-repeats, a TCTA-repeat within the vWFII-3 gene, a TTA-repeat within the PLA-2 gene, and an AAAT-repeat intragenic to the NF1 gene) from human chromosomes 12, 17, and 21, we have detected 21 cases of abnormal segre...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Banchs I,Bosch A,Guimerà J,Lázaro C,Puig A,Estivill X

    更新日期:1994-01-01 00:00:00

  • IL-12Rβ1 deficiency: mutation update and description of the IL12RB1 variation database.

    abstract::IL-12Rβ1 deficiency is an autosomal recessive disorder characterized by predisposition to recurrent and/or severe infections caused by otherwise poorly pathogenic mycobacteria and salmonella. IL-12Rβ1 is a receptor chain of both the IL-12 and the IL-23 receptor and deficiency of IL-12Rβ1 thus abolishes both IL-12 and ...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: van de Vosse E,Haverkamp MH,Ramirez-Alejo N,Martinez-Gallo M,Blancas-Galicia L,Metin A,Garty BZ,Sun-Tan Ç,Broides A,de Paus RA,Keskin Ö,Çağdaş D,Tezcan I,Lopez-Ruzafa E,Aróstegui JI,Levy J,Espinosa-Rosales FJ,Sanal Ö,

    更新日期:2013-10-01 00:00:00

  • Correction of a Cystic Fibrosis Splicing Mutation by Antisense Oligonucleotides.

    abstract::Cystic fibrosis (CF), the most common life-threatening genetic disease in Caucasians, is caused by ∼2,000 different mutations in the CF transmembrane conductance regulator (CFTR) gene. A significant fraction of these (∼13%) affect pre-mRNA splicing for which novel therapies have been somewhat neglected. We have previo...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Igreja S,Clarke LA,Botelho HM,Marques L,Amaral MD

    更新日期:2016-02-01 00:00:00

  • Determination of 30 X-linked adrenoleukodystrophy mutations, including 15 not previously described.

    abstract::X-linked Adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease. It mainly involves the nervous system white matter, adrenal cortex and testes. Several distinct clinical phenotypes are known. The principal biochemical abnormality is the accumulation of saturated very-long-chain fatty acids (VLCFAs : > C...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lachtermacher MB,Seuánez HN,Moser AB,Moser HW,Smith KD

    更新日期:2000-01-01 00:00:00

  • Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in thirteen Spanish families.

    abstract::We have determined the molecular basis of hypoxanthine-guanine phosphoribosyltransferase (HPRT; HPRT1) deficiency in eight Lesch-Nyhan patients and in five partially HPRT deficient patients with mild to severe neurologic symptoms. Eight of these thirteen mutations have not been previously described. HPRT Zaragoza II (...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Torres RJ,Mateos FA,Molano J,Gathoff BS,O'Neill JP,Gundel RM,Trombley L,Puig JG

    更新日期:2000-04-01 00:00:00

  • CAPN5 genetic inactivation phenotype supports therapeutic inhibition trials.

    abstract::Small molecule pharmacological inhibition of dominant human genetic disease is a feasible treatment that does not rely on the development of individual, patient-specific gene therapy vectors. However, the consequences of protein inhibition as a clinical therapeutic are not well-studied. In advance of human therapeutic...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wert KJ,Koch SF,Velez G,Hsu CW,Mahajan M,Bassuk AG,Tsang SH,Mahajan VB

    更新日期:2019-12-01 00:00:00

  • Wolfram syndrome in French population: characterization of novel mutations and polymorphisms in the WFS1 gene.

    abstract::Wolfram syndrome (WS), a rare autosomal recessive neurodegenerative disorder, results in most cases from mutations in the WFS1 gene. In this study, a total of 19 patients with Wolfram syndrome and 36 relatives from 17 families were screened for mutations in the WFS1 gene. WFS1 mutations were identified on both alleles...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Giuliano F,Bannwarth S,Monnot S,Cano A,Chabrol B,Vialettes B,Delobel B,Paquis-Flucklinger V,French Group of WS.

    更新日期:2005-01-01 00:00:00

  • A new polymorphism in the proteolipid protein (PLP1) gene and its use for carrier detection of PLP1 gene duplication in Pelizaeus-Merzbacher disease.

    abstract::Pelizaeus Merzbacher Disease (PMD) is an X-linked recessive dysmyelinating disorder of the central nervous system. Most patients have point mutations in exons of the proteolipid protein (PLP1) gene or duplication of a genomic region that includes the PLP1 gene. We identified a common MspI polymorphism in intron 1 of t...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hobson G,Stabley D,Funanage V,Marks H

    更新日期:2001-02-01 00:00:00

  • A pharmacogenetic approach to identify mutant forms of α-galactosidase A that respond to a pharmacological chaperone for Fabry disease.

    abstract::Fabry disease is caused by mutations in the gene (GLA) that encodes α-galactosidase A (α-Gal A). The iminosugar AT1001 (GR181413A, migalastat hydrochloride, 1-deoxygalactonojirimycin) is a pharmacological chaperone that selectively binds and stabilizes α-Gal A, increasing total cellular levels and activity for some mu...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Wu X,Katz E,Della Valle MC,Mascioli K,Flanagan JJ,Castelli JP,Schiffmann R,Boudes P,Lockhart DJ,Valenzano KJ,Benjamin ER

    更新日期:2011-08-01 00:00:00

  • PCR-based detection of minority point mutations.

    abstract::The need for detection of minority mutations (i.e., a few mutants within a high excess of wild-type alleles) arises frequently in the field of cancer and molecular genetics. Current mutation detection technologies are limited by several technical factors when it comes to the detection of minority point mutations, incl...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Mike Makrigiorgos G

    更新日期:2004-05-01 00:00:00

  • Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature.

    abstract::Developmental and epileptic encephalopathies (DEE) refer to a heterogeneous group of devastating neurodevelopmental disorders. Variants in KCNB1 have been recently reported in patients with early-onset DEE. KCNB1 encodes the α subunit of the delayed rectifier voltage-dependent potassium channel Kv 2.1. We review the 3...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bar C,Barcia G,Jennesson M,Le Guyader G,Schneider A,Mignot C,Lesca G,Breuillard D,Montomoli M,Keren B,Doummar D,Billette de Villemeur T,Afenjar A,Marey I,Gerard M,Isnard H,Poisson A,Dupont S,Berquin P,Meyer P,Gene

    更新日期:2020-01-01 00:00:00

  • Three novel missense mutations in the glucokinase gene (G80S; E221K; G227C) in Italian subjects with maturity-onset diabetes of the young (MODY). Mutations in brief no. 162. Online.

    abstract::The maturity-onset diabetes of the young (MODY), an autosomal dominant form of non-insulin dependent diabetes mellitus (NIDDM), is caused by mutations in the glucokinase (GK, MODY 2) and in the hepatocyte nuclear factor 1a (MODY 3) and 4a (MODY 1) genes. We have screened the glucokinase gene by the polymerase chain re...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Guazzini B,Gaffi D,Mainieri D,Multari G,Cordera R,Bertolini S,Pozza G,Meschi F,Barbetti F

    更新日期:1998-01-01 00:00:00

  • Applying massive parallel sequencing to molecular diagnosis of Marfan and Loeys-Dietz syndromes.

    abstract::The Marfan (MFS) and Loeys-Dietz (LDS) syndromes are caused by mutations in the fibrillin-1 (FBN1) and Transforming Growth Factor Beta Receptor 1 and 2 (TGFBR1 and TGFBR2) genes, respectively. With the current conventional mutation screening technologies, analysis of this set of genes is time consuming and expensive. ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Baetens M,Van Laer L,De Leeneer K,Hellemans J,De Schrijver J,Van De Voorde H,Renard M,Dietz H,Lacro RV,Menten B,Van Criekinge W,De Backer J,De Paepe A,Loeys B,Coucke PJ

    更新日期:2011-09-01 00:00:00