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


: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 families affected by severe hypophosphatasia. Fourteen distinct mutations were found, 3 of which were previously reported in the North American or Japanese populations. Seven of the 11 new mutations were missense mutations (M45L, R119H, G145V, C184Y and H154Y, D289V, E459K), the four others were 2 single nucleotide deletions (544delG and 1172delC), a mutation affecting donor splice site (862 + 5A) and a nonsense mutation (R411X).


Hum Mutat


Human mutation


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





Has Abstract


1999-01-01 00:00:00














  • Exome and genome analysis as a tool for disease identification and treatment: the 2011 Human Genome Variation Society scientific meeting.

    abstract::The 2011 annual scientific meeting of the Human Genome Variation Society (HGVS) was held on the 11th of October, in Montreal, Canada. The theme of this meeting was "Exome and Genome Analysis as a Tool for Disease Identification and Treatment." In the last few years, there has been a substantial increase in the use of ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Oetting WS

    更新日期:2012-03-01 00:00:00

  • Screening of thiopurine S-methyltransferase mutations by horizontal conformation-sensitive gel electrophoresis.

    abstract::The genetic polymorphism of thiopurine S-methyltransferase (TPMT) has had a highly significant clinical impact due to its association with individual variation in the toxicity and therapeutic efficiency of thiopurine drugs, which are pharmaceutical agents widely used in the treatment of several kinds of diseases. Unti...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Alves S,Prata MJ,Ferreira F,Amorim A

    更新日期:2000-01-01 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

  • Analysis of RAD51C germline mutations in high-risk breast and ovarian cancer families and ovarian cancer patients.

    abstract::There is strong evidence that overtly inactivating mutations in RAD51C predispose to hereditary breast and ovarian cancer but the prevalence of such mutations, and whether they are associated with a particular clinical phenotype, remains unclear. Resolving these questions has important implications for the implementat...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Thompson ER,Boyle SE,Johnson J,Ryland GL,Sawyer S,Choong DY,kConFab,Chenevix-Trench G,Trainer AH,Lindeman GJ,Mitchell G,James PA,Campbell IG

    更新日期:2012-01-01 00:00:00

  • Human Variome Project country nodes: documenting genetic information within a country.

    abstract::The Human Variome Project ( is an international effort aiming to systematically collect and share information on all human genetic variation. The two main pillars of this effort are gene/disease-specific databases and a network of Human Variome Project Country Nodes. The latter are n...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Patrinos GP,Smith TD,Howard H,Al-Mulla F,Chouchane L,Hadjisavvas A,Hamed SA,Li XT,Marafie M,Ramesar RS,Ramos FJ,de Ravel T,El-Ruby MO,Shrestha TR,Sobrido MJ,Tadmouri G,Witsch-Baumgartner M,Zilfalil BA,Auerbach AD,Ca

    更新日期:2012-11-01 00:00:00

  • Molecular basis of familial hypercholesterolemia in Brazil: Identification of seven novel LDLR gene mutations.

    abstract::Low-density lipoprotein receptor (LDLR) gene mutations cause familial hypercholesterol-emia (FH), one of the most common single gene disorders. The spectrum of LDLR mutations in Brazil is not known. The aim of this study was the characterization of LDLR mutations in 35 unrelated Brazilian patients with heterozygous FH...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Salazar LA,Hirata MH,Cavalli SA,Nakandakare ER,Forti N,Diament J,Giannini SD,Bertolami MC,Hirata RD

    更新日期:2002-04-01 00:00:00

  • Transcript dosage effect in familial adenomatous polyposis: model offered by two kindreds with exon 9 APC gene mutations.

    abstract::Analysis of genotype-phenotype correlations in familial adenomatous polyposis (FAP) patients demonstrated that the phenotypic heterogeneity of FAP is partly related to the mutation site. We investigated the molecular basis for the difference in severity of colorectal disease observed comparing FAP patients from two ki...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Curia MC,Esposito DL,Aceto G,Palmirotta R,Crognale S,Valanzano R,Ficari F,Tonelli F,Battista P,Mariani-Costantini R,Cama A

    更新日期:1998-01-01 00:00:00

  • Targeted resequencing reveals genetic risks in patients with sporadic idiopathic pulmonary fibrosis.

    abstract::Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. However, a large fraction of genetic cause remains unexplained, especially in sporadic IPF (∼80% IPF). By systemically reviewing related literature and potential pathogenic pathways, 92 potentially IPF-relate...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Deng Y,Li Z,Liu J,Wang Z,Cao Y,Mou Y,Fu B,Mo B,Wei J,Cheng Z,Luo L,Li J,Shu Y,Wang X,Luo G,Yang S,Wang Y,Zhu J,Yang J,Wu M,Xu X,Ge R,Chen X,Peng Q,Wei G,Li Y,Yang H,Fang S,Zhang X,Xiong W

    更新日期:2018-09-01 00:00:00

  • The distribution of constitutional and somatic mutations in the neurofibromatosis 2 gene.

    abstract::Constitutional heterozygous inactivating mutations in the neurofibromatosis 2 (NF2) tumor suppressor gene cause the autosomal dominant disease NF2, and biallelic inactivating somatic NF2 mutations are found in a high proportion of unilateral sporadic vestibular schwannoma (USVS) and sporadic meningioma. We surveyed th...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Baser ME,Contributors to the International NF2 Mutation Database.

    更新日期:2006-04-01 00:00:00

  • Sequence variation in the ATP-binding domain of the Wilson disease transporter, ATP7B, affects copper transport in a yeast model system.

    abstract::ATP7B is a copper transporting P-type ATPase defective in the autosomal recessive copper storage disorder, Wilson disease (WND). Functional assessment of variants helps to distinguish normal from disease-causing variants and provides information on important amino acid residues. A total of 11 missense variants of ATP7...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hsi G,Cullen LM,Macintyre G,Chen MM,Glerum DM,Cox DW

    更新日期:2008-04-01 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

  • 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

  • Functional analyses of human and zebrafish 18-amino acid in-frame deletion pave the way for domain mapping of the cerebral cavernous malformation 3 protein.

    abstract::Cerebral cavernous malformations (CCMs) may cause recurrent headaches, seizures, and hemorrhagic stroke and have been associated with loss-of-function mutations in CCM1/KRIT1, CCM2, and CCM3/programmed cell death 10 (PDCD10). The CCM3/PDCD10 amino acid sequence does not reveal significant homologies to protein domains...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Voss K,Stahl S,Hogan BM,Reinders J,Schleider E,Schulte-Merker S,Felbor U

    更新日期:2009-06-01 00:00:00

  • Unique aspects of sequence variant interpretation for inborn errors of metabolism (IEM): The ClinGen IEM Working Group and the Phenylalanine Hydroxylase Gene.

    abstract::The ClinGen Inborn Errors of Metabolism Working Group was tasked with creating a comprehensive, standardized knowledge base of genes and variants for metabolic diseases. Phenylalanine hydroxylase (PAH) deficiency was chosen to pilot development of the Working Group's standards and guidelines. A PAH variant curation ex...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Zastrow DB,Baudet H,Shen W,Thomas A,Si Y,Weaver MA,Lager AM,Liu J,Mangels R,Dwight SS,Wright MW,Dobrowolski SF,Eilbeck K,Enns GM,Feigenbaum A,Lichter-Konecki U,Lyon E,Pasquali M,Watson M,Blau N,Steiner RD,Craige

    更新日期:2018-11-01 00:00:00

  • Tissue distribution of the ND4/11778 mutation in heteroplasmic lineages with Leber hereditary optic neuropathy.

    abstract::Leber hereditary optic neuropathy (LHON) is a maternally inherited eye disease most commonly caused by mitochondrial DNA (mtDNA) point mutation at position 11778, 3460, or 14484. Approximately 14% of families show heteroplasmy for the pathogenic mutations but little is known about the mutational burden in different ti...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Juvonen V,Nikoskelainen E,Lamminen T,Penttinen M,Aula P,Savontaus ML

    更新日期:1997-01-01 00:00:00

  • Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9-related disease.

    abstract::MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness, presenile cataracts,...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Pecci A,Panza E,Pujol-Moix N,Klersy C,Di Bari F,Bozzi V,Gresele P,Lethagen S,Fabris F,Dufour C,Granata A,Doubek M,Pecoraro C,Koivisto PA,Heller PG,Iolascon A,Alvisi P,Schwabe D,De Candia E,Rocca B,Russo U,Rameng

    更新日期:2008-03-01 00:00:00

  • Splice-site mutation in the PDS gene may result in intrafamilial variability for deafness in Pendred syndrome.

    abstract::Pendred syndrome is a recessive inherited disorder that consists of developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement (goiter). This disorder may account for up to 10% of cases of hereditary deafness. The disease gene (PDS) has been mapped to chromosome 7q22-q31, a...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: López-Bigas N,Rabionet R,de Cid R,Govea N,Gasparini P,Zelante L,Arbonés ML,Estivill X

    更新日期:1999-01-01 00:00:00

  • Describing structural changes by extending HGVS sequence variation nomenclature.

    abstract::New technologies allow rapid discovery of novel sequence variants among which those involving complex structural rearrangements. The description of such complex variants challenges the existing standard sequence variation nomenclature of the Human Genome Variation Society (HGVS,, because ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Taschner PE,den Dunnen JT

    更新日期:2011-05-01 00:00:00

  • Exon skipping mutations in collagen VI are common and are predictive for severity and inheritance.

    abstract::Mutations in the genes encoding collagen VI (COL6A1, COL6A2, and COL6A3) cause Bethlem myopathy (BM) and Ullrich congenital muscular dystrophy (UCMD), two related conditions of differing severity. BM is a relatively mild dominantly inherited disorder characterized by proximal weakness and distal joint contractures. UC...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lampe AK,Zou Y,Sudano D,O'Brien KK,Hicks D,Laval SH,Charlton R,Jimenez-Mallebrera C,Zhang RZ,Finkel RS,Tennekoon G,Schreiber G,van der Knaap MS,Marks H,Straub V,Flanigan KM,Chu ML,Muntoni F,Bushby KM,Bönnemann CG

    更新日期:2008-06-01 00:00:00

  • Genetic and functional analyses of ZIC3 variants in congenital heart disease.

    abstract::Mutations in zinc-finger in cerebellum 3 (ZIC3) result in heterotaxy or isolated congenital heart disease (CHD). The majority of reported mutations cluster in zinc-finger domains. We previously demonstrated that many of these lead to aberrant ZIC3 subcellular trafficking. A relative paucity of N- and C-terminal mutati...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cowan J,Tariq M,Ware SM

    更新日期:2014-01-01 00:00:00

  • Identification of novel mutations in PEX2, PEX6, PEX10, PEX12, and PEX13 in Zellweger spectrum patients.

    abstract::Mutations in each of the 13 identified human PEX genes are known to cause a peroxisomal biogenesis defect (PBD). Affected patients can be divided into two broad clinical spectra: the Zellweger spectrum, which accounts for about 80% of PBD patients, and the rhizomelia chondrodysplasia punctata (RCDP) spectrum. The clin...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Krause C,Rosewich H,Thanos M,Gärtner J

    更新日期:2006-11-01 00:00:00

  • Stability related bias in residues replacing glycines within the collagen triple helix (Gly-Xaa-Yaa) in inherited connective tissue disorders.

    abstract::A missense mutation leading to the replacement of one Gly in the (Gly-Xaa-Yaa)n repeat of the collagen triple helix can cause a range of heritable connective tissue disorders that depend on the gene in which the mutation occurs. Osteogenesis imperfecta results from mutations in type I collagen, Ehlers-Danlos syndrome ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Persikov AV,Pillitteri RJ,Amin P,Schwarze U,Byers PH,Brodsky B

    更新日期:2004-10-01 00:00:00

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

    abstract::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 geneticis...

    journal_title:Human mutation



    authors: Smith A,Boycott KM,Jarinova O

    更新日期:2014-02-01 00:00:00

  • A novel frameshift mutation (141delT) in exon 1 of the 21-hydroxylase gene (CYP21) in a patient with the salt wasting form of congenital adrenal hyperplasia. Mutation in brief no. 255. Online.

    abstract::Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disease with a wide range of clinical manifestation. In 90-95% of the cases it is caused by 21-hydroxylase deficiency (OMIM #201910) due to mutations of the CYP21 gene (GDB Accession #M12792). In most cases the CYP21-inactivating point mutations are ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Krone N,Braun A,Roscher AA,Schwarz HP

    更新日期:1999-01-01 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

  • Novel mutations and SNPs identified in CCR2 using a new comprehensive denaturing gradient gel electrophoresis assay.

    abstract::A single nucleotide polymorphism (SNP) at codon 64 in the CC chemokine receptor 2 gene (CCR2 V64I) has been associated with a dominant effect of delaying disease progression from human immunodeficiency virus-1 (HIV-1) infection to acquired immunodeficiency syndrome (AIDS). The objective of our study was to design a co...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Petersen DC,Laten A,Zeier MD,Grimwood A,Rensburg EJ,Hayes VM

    更新日期:2002-10-01 00:00:00

  • Molecular basis of congenital erythropoietic porphyria: mutations in the human uroporphyrinogen III synthase gene.

    abstract::Congenital erythropoietic porphyria (CEP) is an autosomal recessive inborn error of metabolism that results from the markedly deficient activity of the fourth enzyme in the heme biosynthetic pathway, uroporphyrinogen III synthase (URO-synthase). To date, 17 mutations have been described including 11 missense, one nons...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Xu W,Astrin KH,Desnick RJ

    更新日期:1996-01-01 00:00:00

  • CACNA1H variants are not a cause of monogenic epilepsy.

    abstract::CACNA1H genetic variants were originally reported in a childhood absence epilepsy cohort. Subsequently, genetic testing for CACNA1H became available and is currently offered by commercial laboratories. However, the current status of CACNA1H as a monogenic cause of epilepsy is controversial, highlighted by ClinGen's re...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Calhoun JD,Huffman AM,Bellinski I,Kinsley L,Bachman E,Gerard E,Kearney JA,Carvill GL

    更新日期:2020-06-01 00:00:00

  • PCDH19-related infantile epileptic encephalopathy: an unusual X-linked inheritance disorder.

    abstract::PCDH19 encodes protocadherin 19 on chromosome Xq22.3. This 1,148-amino-acid protein, highly expressed during brain development, could play significant roles in neuronal migration or establishment of synaptic connections. PCDH19 is composed of six exons, with a large first exon encoding the entire extracellular domain ...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Depienne C,LeGuern E

    更新日期:2012-04-01 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