Transthyretin mutations in health and disease.


:To date, over 40 different mutations in transthyretin (TTR) have been associated with amyloid deposition. The major unresolved problem is the correlation between the clinical heterogeneity and the genetic heterogeneity. For instance, whereas some mutations produce neuropathy and some give rise to cardiomyopathy, others produce vitreous opacities, the vast majority being neuropathic. Moreover, some mutations are not amyloidogenic but are responsible to hyperthyroxinemias (by virtue of the protein function in thyroid transport), whereas others are apparently nonpathogenic. The study of TTR variants is very important to the understanding of the amyloid formation process and to establish a relationship between the structure and function of the molecule. The results of current TTR mutation screening programs and their characterization are summarized.


Hum Mutat


Human mutation


Saraiva MJ




Has Abstract


1995-01-01 00:00:00












  • Large differences in proportions of harmful and benign amino acid substitutions between proteins and diseases.

    abstract::Genes and proteins are known to have differences in their sensitivity to alterations. Despite numerous sequencing studies, proportions of harmful and harmless substitutions are not known for proteins and groups of proteins. To address this question, we predicted the outcome for all possible single amino acid substitut...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Schaafsma GCP,Vihinen M

    更新日期:2017-07-01 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

  • Copy number variation at the FCGR locus includes FCGR3A, FCGR2C and FCGR3B but not FCGR2A and FCGR2B.

    abstract::Human Fcgamma receptors (FcgammaRs) are glycoproteins that bind the Fc region of IgG. The genes encoding the low-affinity FcgammaRs are located on chromosome 1q23-24. Beside single nucleotide polymorphisms (SNPs), gene copy number variation (CNV) is now being recognized as an important indicator for inter-individual d...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Breunis WB,van Mirre E,Geissler J,Laddach N,Wolbink G,van der Schoot E,de Haas M,de Boer M,Roos D,Kuijpers TW

    更新日期:2009-05-01 00:00:00

  • Genetic lesions of bilirubin uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) causing Crigler-Najjar and Gilbert syndromes: correlation of genotype to phenotype.

    abstract::Uridine-diphosphoglucuronate glucuronosyltransferases (UGTs) are a family of enzymes that conjugate various endogenous and exogenous compounds with glucuronic acid and facilitate their excretion in the bile. Bilirubin-UGT(1) (UGT1A1) is the only isoform that significantly contributes to the conjugation of bilirubin. L...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Kadakol A,Ghosh SS,Sappal BS,Sharma G,Chowdhury JR,Chowdhury NR

    更新日期:2000-10-01 00:00:00

  • Enigmatic in vivo iduronate-2-sulfatase (IDS) mutant transcript correction to wild-type in Hunter syndrome.

    abstract::Sequence analysis of the X-linked iduronate-2-sulfatase (IDS) gene in two Hunter syndrome patients revealed a lack of concordance between IDS genomic DNA and cDNA. These individuals were found to be hemizygous respectively for a nonsense mutation [c.22C>T;p.R8X] and a frameshift micro-insertion [c.10insT;p.P4Sfs] in t...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lualdi S,Tappino B,Di Duca M,Dardis A,Anderson CJ,Biassoni R,Thompson PW,Corsolini F,Di Rocco M,Bembi B,Regis S,Cooper DN,Filocamo M

    更新日期:2010-04-01 00:00:00

  • Three novel thiopurine S-methyltransferase allelic variants (TPMT*20, *21, *22) - association with decreased enzyme function.

    abstract::The genetic polymorphism of the thiopurine S-methyltransferase, TPMT, comprises at least 21 alleles causing three distinct drug metabolism phenotypes termed normal/high, intermediate, and deficient methylators. In consequence, adverse drug reactions may occur if standard doses of thiopurines are applied routinely. Gen...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Schaeffeler E,Eichelbaum M,Reinisch W,Zanger UM,Schwab M

    更新日期:2006-09-01 00:00:00

  • Deficiency in DNA mismatch repair increases the rate of telomere shortening in normal human cells.

    abstract::DNA mismatch repair (MMR) is essential for genome stability and inheritance of a mutated MMR gene, most frequently MSH2 or MLH1, results in cancer predisposition known as Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC). Tumors that arise through MMR deficiency show instability at simple tandem repe...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mendez-Bermudez A,Royle NJ

    更新日期:2011-08-01 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

  • A mutation update on the LDS-associated genes TGFB2/3 and SMAD2/3.

    abstract::The Loeys-Dietz syndrome (LDS) is a connective tissue disorder affecting the cardiovascular, skeletal, and ocular system. Most typically, LDS patients present with aortic aneurysms and arterial tortuosity, hypertelorism, and bifid/broad uvula or cleft palate. Initially, mutations in transforming growth factor-β (TGF-β...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Schepers D,Tortora G,Morisaki H,MacCarrick G,Lindsay M,Liang D,Mehta SG,Hague J,Verhagen J,van de Laar I,Wessels M,Detisch Y,van Haelst M,Baas A,Lichtenbelt K,Braun K,van der Linde D,Roos-Hesselink J,McGillivray G,M

    更新日期:2018-05-01 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 CLCN5 pathogenic mutation supports Dent disease with normal endosomal acidification.

    abstract::Dent disease is an X-linked recessive renal tubular disorder characterized by low-molecular-weight proteinuria, hypercalciuria, nephrolithiasis, nephrocalcinosis, and progressive renal failure. Inactivating mutations of CLCN5, the gene encoding the 2Cl- /H+ exchanger ClC-5, have been reported in patients with Dent dis...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bignon Y,Alekov A,Frachon N,Lahuna O,Jean-Baptiste Doh-Egueli C,Deschênes G,Vargas-Poussou R,Lourdel S

    更新日期:2018-08-01 00:00:00

  • Quantification of Phenotype Information Aids the Identification of Novel Disease Genes.

    abstract::Next-generation sequencing led to the identification of many potential novel disease genes. The presence of mutations in the same gene in multiple unrelated patients is, however, a priori insufficient to establish that these genes are truly involved in the respective disease. Here, we show how phenotype information ca...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Vulto-van Silfhout AT,Gilissen C,Goeman JJ,Jansen S,van Amen-Hellebrekers CJM,van Bon BWM,Koolen DA,Sistermans EA,Brunner HG,de Brouwer APM,de Vries BBA

    更新日期:2017-05-01 00:00:00

  • BBS7 and TTC8 (BBS8) mutations play a minor role in the mutational load of Bardet-Biedl syndrome in a multiethnic population.

    abstract::Bardet Biedl syndrome is a genetically heterogeneous ciliopathy with fourteen genes currently identified. To date, mutations in BBS7 and TTC8 (BBS8) were reported in 4.2% and 2.8% of BBS families respectively. We sequenced the coding regions of BBS7 and TTC8 in 35 BBS families of diverse ancestral backgrounds. In addi...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bin J,Madhavan J,Ferrini W,Mok CA,Billingsley G,Héon E

    更新日期:2009-07-01 00:00:00

  • Somatic mutations of the first 14 exons of APC in hamartomatous polyps of the colon.

    abstract::Although hamartomatous or hyperplastic polyps are rarely accompanied by adenomatous or carcinomatous foci, the role of APC (MIM# 175100) mutations in these polyps is not clear. The neoplastic potential of these polyps was assessed with regard to somatic mutation of the first 14 exons of APC. DNA from 14 hamartomatous ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Kim JC,Roh SA,Kim HC,Yu CS,Lee DH,Ahn BY,Kim KM,Yang SK,Kang GH,Beck NE,Bodmer WF

    更新日期:1999-10-01 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

  • Assessing how reduced expression levels of the mismatch repair genes MLH1, MSH2, and MSH6 affect repair efficiency.

    abstract::Lynch syndrome (LS), the most common familial colon cancer, is associated with mismatch repair (MMR) malfunction. As mutation carriers inherit one normal and one defected MMR gene allele, cancer risk can be considered as limited amount of normal MMR gene product. How reductions in different MMR gene expressions affect...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Kansikas M,Kasela M,Kantelinen J,Nyström M

    更新日期:2014-09-01 00:00:00

  • GCK and HNF1A mutations in Canadian families with maturity onset diabetes of the young (MODY).

    abstract::Maturity onset diabetes of the young (MODY) is a genetically heterogeneous form of type 2 diabetes that is characterized by autosomal dominant inheritance, onset in early adulthood and a primary defect in insulin secretion. Mutations in at least six genes have been shown to underlie MODY, including mutations in GCK (e...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cao H,Shorey S,Robinson J,Metzger DL,Stewart L,Cummings E,Hegele RA

    更新日期:2002-12-01 00:00:00

  • MEFV mutations in Behçet's disease.

    abstract::Familial Mediterranean fever (FMF) and Behçet's disease (BD), both inflammatory diseases, are highly prevalent in the Middle Eastern and Mediterranean populations. FMF is a Mendelian autosomic recessive disease linked to MEFV, a gene of unknown function. BD in contrast is a polyfactorial disease associated with the ma...

    journal_title:Human mutation

    pub_type: 杂志文章,多中心研究


    authors: Touitou I,Magne X,Molinari N,Navarro A,Quellec AL,Picco P,Seri M,Ozen S,Bakkaloglu A,Karaduman A,Garnier JM,Demaille J,Koné-Paut I

    更新日期:2000-09-01 00:00:00

  • Impaired development of neural-crest cell-derived organs and intellectual disability caused by MED13L haploinsufficiency.

    abstract::MED13L is a component subunit of the Mediator complex, an important regulator of transcription that is highly conserved across eukaryotes. Here, we report MED13L disruption in a translocation t(12;19) breakpoint of a patient with Pierre-Robin syndrome, moderate intellectual disability, craniofacial anomalies, and musc...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Utami KH,Winata CL,Hillmer AM,Aksoy I,Long HT,Liany H,Chew EG,Mathavan S,Tay SK,Korzh V,Sarda P,Davila S,Cacheux V

    更新日期:2014-11-01 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

  • Whole-Genome Sequencing and Integrative Genomic Analysis Approach on Two 22q11.2 Deletion Syndrome Family Trios for Genotype to Phenotype Correlations.

    abstract::The 22q11.2 deletion syndrome (22q11DS) affects 1:4,000 live births and presents with highly variable phenotype expressivity. In this study, we developed an analytical approach utilizing whole-genome sequencing (WGS) and integrative analysis to discover genetic modifiers. Our pipeline combined available tools in order...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chung JH,Cai J,Suskin BG,Zhang Z,Coleman K,Morrow BE

    更新日期:2015-08-01 00:00:00

  • Detection of thirty novel FBN1 mutations in patients with Marfan syndrome or a related fibrillinopathy.

    abstract::Marfan syndrome (MFS) is a disorder of the extracellular matrix caused by mutations in the gene encoding fibrillin-1 (FBN1). Recent studies have illustrated the variability in disease severity and clinical manifestations of MFS. Useful genotype-phenotype correlations have been slow to emerge. We screened 57 unrelated ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Biggin A,Holman K,Brett M,Bennetts B,Adès L

    更新日期:2004-01-01 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

  • TP53 and head and neck neoplasms.

    abstract::Head and neck cancer is an important health problem around the world, accounting for approximately 500,000 new cases each year of head and neck squamous cell carcinoma (HNSCC). Carcinogenesis of head and neck results from a dysregulation of cellular proliferation, differentiation, and cell death. The major etiologic a...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Blons H,Laurent-Puig P

    更新日期:2003-03-01 00:00:00

  • STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility.

    abstract::SH3 and cysteine-rich domain-containing protein 3 (STAC3) is an essential component of the skeletal muscle excitation-contraction coupling (ECC) machinery, though its role and function are not yet completely understood. Here, we report 18 patients carrying a homozygous p.(Trp284Ser) STAC3 variant in addition to a pati...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Zaharieva IT,Sarkozy A,Munot P,Manzur A,O'Grady G,Rendu J,Malfatti E,Amthor H,Servais L,Urtizberea JA,Neto OA,Zanoteli E,Donkervoort S,Taylor J,Dixon J,Poke G,Foley AR,Holmes C,Williams G,Holder M,Yum S,Medne L

    更新日期:2018-12-01 00:00:00

  • Higher-than-expected population prevalence of potentially pathogenic germline TP53 variants in individuals unselected for cancer history.

    abstract::Li-Fraumeni syndrome (LFS) is an autosomal-dominant cancer predisposition disorder associated with pathogenic germline variants in TP53, with a high penetrance over an individual's lifetime. The actual population prevalence of pathogenic germline TP53 mutations is still unclear, most likely due to biased selection of ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: de Andrade KC,Mirabello L,Stewart DR,Karlins E,Koster R,Wang M,Gapstur SM,Gaudet MM,Freedman ND,Landi MT,Lemonnier N,Hainaut P,Savage SA,Achatz MI

    更新日期:2017-12-01 00:00:00

  • NR5A1 gene variants repress the ovarian-specific WNT signaling pathway in 46,XX disorders of sex development patients.

    abstract::Several recent reports have described a missense variant in the gene NR5A1 (c.274C>T; p.Arg92Trp) in a significant number of 46,XX ovotesticular or testicular disorders of sex development (DSDs) cases. The affected residue falls within the DNA-binding domain of the NR5A1 protein, however the exact mechanism by which i...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Knarston IM,Robevska G,van den Bergen JA,Eggers S,Croft B,Yates J,Hersmus R,Looijenga LHJ,Cameron FJ,Monhike K,Ayers KL,Sinclair AH

    更新日期:2019-02-01 00:00:00

  • Overexpression of the C-type natriuretic peptide (CNP) is associated with overgrowth and bone anomalies in an individual with balanced t(2;7) translocation.

    abstract::Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. We report the molecular characterization of a de novo balanced t(2;7)(q37.1;q21.3) tr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Bocciardi R,Giorda R,Buttgereit J,Gimelli S,Divizia MT,Beri S,Garofalo S,Tavella S,Lerone M,Zuffardi O,Bader M,Ravazzolo R,Gimelli G

    更新日期:2007-07-01 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

  • 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