Pancreatic insufficiency and pulmonary disease in German and Slavic cystic fibrosis patients with the R347P mutation.


:Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) that codes for a cAMP-regulated chloride channel. The R347P is a missense mutation located within the first membrane spanning domain (MSD1) of the CFTR protein. This mutation occurs with an overall worldwide frequency of about 0.2%. The patients, originally described with this mutation were compound heterozygotes with the delta F508 mutation and had a very mild course of CF, suggesting that R347P, similar to other missense mutations affecting the MSD1 domain, causes a mild phenotype. We report here a group of 19 CF patients with the R347P mutation of German, Bulgarian, Czech, and Slovak origin, including two homozygotes. Most patients presented with early disease onset, pancreas insufficiency (PI), and early pulmonary involvement, suggesting that this mutation can lead to a severe course of CF. Most R347P alleles in the group studied share a common polymorphic haplotype. In addition, these analyses gave evidence for recurrence of the mutation in two CF patients of German and Czech origin.


Hum Mutat


Human mutation


Varon R,Stuhrmann M,Macek M Jr,Kufardjieva A,Angelicheva D,Magdorf K,Jordanova A,Savov A,Wahn U,Macek M




Has Abstract,Author List Incomplete


1995-01-01 00:00:00












  • Biochemical and molecular characterization of 18 patients with pyridoxine-dependent epilepsy and mutations of the antiquitin (ALDH7A1) gene.

    abstract::Patients with pyridoxine dependent epilepsy (PDE) present with early-onset seizures resistant to common anticonvulsants. According to the benefit of pyridoxine (vitamin B(6)) and recurrence of seizures on pyridoxine withdrawal, patients so far have been classified as having definite, probable, or possible PDE. Recentl...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Plecko B,Paul K,Paschke E,Stoeckler-Ipsiroglu S,Struys E,Jakobs C,Hartmann H,Luecke T,di Capua M,Korenke C,Hikel C,Reutershahn E,Freilinger M,Baumeister F,Bosch F,Erwa W

    更新日期:2007-01-01 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

  • A double-variant transthyretin allele (Ser 6, Ile 33) in the Israeli patient "SKO" with familial amyloidotic polyneuropathy.

    abstract::Transthyretin (TTR) isolated from amyloid fibrils from an Israeli patient ("SKO") with familial amyloidotic polyneuropathy has been studied by two groups of investigators. Originally, a position 49 Thr-->Gly substitution was reported; subsequently, a position 33 Phe-->Ile substitution was found instead. We have studie...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Jacobson DR,Buxbaum JN

    更新日期:1994-01-01 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

  • EYS is a major gene for rod-cone dystrophies in France.

    abstract::Autosomal-recessive retinitis pigmentosa (arRP) was recently associated with mutations in a novel gene EYS, spanning over 2 Mb, making it the largest known gene expressed in the human eye. The purpose of this study was to establish the prevalence and nature of EYS mutations in a clinically well-characterized cohort of...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Audo I,Sahel JA,Mohand-Saïd S,Lancelot ME,Antonio A,Moskova-Doumanova V,Nandrot EF,Doumanov J,Barragan I,Antinolo G,Bhattacharya SS,Zeitz C

    更新日期:2010-05-01 00:00:00

  • Pathogenic mitochondrial tRNA mutations--which mutations are inherited and why?

    abstract::Mitochondrial transfer RNA (mt-tRNA) mutations are the commonest mitochondrial (mtDNA) mutations to cause human disease. The majority of mt-tRNA mutations are heteroplasmic and while some exhibit maternal transmission within families, many others are only seen as sporadic mutations. Using the available clinical, bioch...

    journal_title:Human mutation

    pub_type: 杂志文章,meta分析


    authors: Elson JL,Swalwell H,Blakely EL,McFarland R,Taylor RW,Turnbull DM

    更新日期:2009-11-01 00:00:00

  • Familial lipoprotein lipase (LPL) deficiency: a catalogue of LPL gene mutations identified in 20 patients from the UK, Sweden, and Italy.

    abstract::The aim of this study was to identify mutations in the lipoprotein lipase (LPL) gene in 20 unrelated patients with familial lipoprotein deficiency (FLLD) and to investigate the genotype/phenotype relationship. The previously reported G188E mutation (Monsalve et al., J Clin Invest 86:728-734, 1990) was screened for and...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Mailly F,Palmen J,Muller DP,Gibbs T,Lloyd J,Brunzell J,Durrington P,Mitropoulos K,Betteridge J,Watts G,Lithell H,Angelico F,Humphries SE,Talmud PJ

    更新日期:1997-01-01 00:00:00

  • An overview and update of ATP7A mutations leading to Menkes disease and occipital horn syndrome.

    abstract::Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar "kinky" hair, are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority of patients are males. M...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Tümer Z

    更新日期:2013-03-01 00:00:00

  • MSeqDR: A Centralized Knowledge Repository and Bioinformatics Web Resource to Facilitate Genomic Investigations in Mitochondrial Disease.

    abstract::MSeqDR is the Mitochondrial Disease Sequence Data Resource, a centralized and comprehensive genome and phenome bioinformatics resource built by the mitochondrial disease community to facilitate clinical diagnosis and research investigations of individual patient phenotypes, genomes, genes, and variants. A central Web ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Shen L,Diroma MA,Gonzalez M,Navarro-Gomez D,Leipzig J,Lott MT,van Oven M,Wallace DC,Muraresku CC,Zolkipli-Cunningham Z,Chinnery PF,Attimonelli M,Zuchner S,Falk MJ,Gai X

    更新日期:2016-06-01 00:00:00

  • Characterization of two arylsulfatase A missense mutations D335V and T274M causing late infantile metachromatic leukodystrophy.

    abstract::Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. We describe a novel missense mutation in exon 6 causing the substitution of Asp335 by Val. In transient transfections no enzyme activity could be expressed from the arylsulfatase A cDNA carrying this mutation. Exa...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Hess B,Kafert S,Heinisch U,Wenger DA,Zlotogora J,Gieselmann V

    更新日期:1996-01-01 00:00:00

  • 11q13 is a susceptibility locus for hormone receptor positive breast cancer.

    abstract::A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10, and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we genotyped the variants ...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Lambrechts D,Truong T,Justenhoven C,Humphreys MK,Wang J,Hopper JL,Dite GS,Apicella C,Southey MC,Schmidt MK,Broeks A,Cornelissen S,van Hien R,Sawyer E,Tomlinson I,Kerin M,Miller N,Milne RL,Zamora MP,Pérez JI,Beníte

    更新日期:2012-07-01 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

  • The novel p.Ser263Phe mutation in the human high-affinity choline transporter 1 (CHT1/SLC5A7) causes a lethal form of fetal akinesia syndrome.

    abstract::A subset of a larger and heterogeneous class of disorders, the congenital myasthenic syndromes (CMS) are caused by pathogenic variants in genes encoding proteins that support the integrity and function of the neuromuscular junction (NMJ). A central component of the NMJ is the sodium-dependent high-affinity choline tra...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Banerjee M,Arutyunov D,Brandwein D,Janetzki-Flatt C,Kolski H,Hume S,Leonard NJ,Watt J,Lacson A,Baradi M,Leslie EM,Cordat E,Caluseriu O

    更新日期:2019-10-01 00:00:00

  • An online locus-specific mutation database for familial hypertrophic cardiomyopathy.

    abstract::The aim of this locus-specific mutation database was to provide an online resource that contains summarised and updated information on familial hypertrophic cardiomyopathy (FHC)-associated mutations and related data, for researchers and clinicians. It also serves as a means of publishing previously unpublished data, w...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Fung DC,Yu B,Littlejohn T,Trent RJ

    更新日期:1999-01-01 00:00:00

  • Determining sequence length or content in zero, one, and two dimensions.

    abstract::High-throughput assays are essential for the practical application of mutation detection in medicine and research. Moreover, such assays should produce informative data of high quality that have a low-error rate and a low cost. Unfortunately, this is not currently the case. Instead, we typically witness legions of peo...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Perlin MW,Szabady B

    更新日期:2002-04-01 00:00:00

  • wKinMut-2: Identification and Interpretation of Pathogenic Variants in Human Protein Kinases.

    abstract::Most genomic alterations are tolerated while only a minor fraction disrupts molecular function sufficiently to drive disease. Protein kinases play a central biological function and the functional consequences of their variants are abundantly characterized. However, this heterogeneous information is often scattered acr...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Vazquez M,Pons T,Brunak S,Valencia A,Izarzugaza JM

    更新日期:2016-01-01 00:00:00

  • Exon scanning of the entire TSC2 gene for germline mutations in 40 unrelated patients with tuberous sclerosis.

    abstract::Tuberous sclerosis complex (TSC) is a dominantly inherited multisystem disorder resulting in the development of hamartomatous growths in many organs. Genetic heterogeneity has been demonstrated linking the familial cases to either TSC1 at 9q34.3, or TSC2 at 16p13.3. About two-thirds of the TSC cases are sporadic and a...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Beauchamp RL,Banwell A,McNamara P,Jacobsen M,Higgins E,Northrup H,Short P,Sims K,Ozelius L,Ramesh V

    更新日期:1998-01-01 00:00:00

  • Mosaicism for dominant collagen 6 mutations as a cause for intrafamilial phenotypic variability.

    abstract::Collagen 6-related dystrophies and myopathies (COL6-RD) are a group of disorders that form a wide phenotypic spectrum, ranging from severe Ullrich congenital muscular dystrophy, intermediate phenotypes, to the milder Bethlem myopathy. Both inter- and intrafamilial variable expressivity are commonly observed. We presen...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Donkervoort S,Hu Y,Stojkovic T,Voermans NC,Foley AR,Leach ME,Dastgir J,Bolduc V,Cullup T,de Becdelièvre A,Yang L,Su H,Meilleur K,Schindler AB,Kamsteeg EJ,Richard P,Butterfield RJ,Winder TL,Crawford TO,Weiss RB,Mun

    更新日期:2015-01-01 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

  • A comprehensive scanning method for rapid detection of beta-globin gene mutations and polymorphisms.

    abstract::We describe a scanning procedure for the detection of beta-globin gene mutations and the prenatal diagnosis of beta-thalassemias. The method is based on the combined use of PCR and denaturing gradient gel electrophoresis (DGGE) of six amplified fragments encompassing the whole beta-globin coding region and splice junc...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Ghanem N,Girodon E,Vidaud M,Martin J,Fanen P,Plassa F,Goossens M

    更新日期:1992-01-01 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

  • miRNA genes and the brain: implications for psychiatric disorders.

    abstract::MicroRNAs (miRNAs) are a class of nonprotein coding genes with a growing importance in regulatory mechanisms of gene expression related to brain function and plasticity. Considering the relative lack of success of the analysis of variations in candidate protein coding genes and of genome-wide association studies to id...

    journal_title:Human mutation

    pub_type: 杂志文章,评审


    authors: Forero DA,van der Ven K,Callaerts P,Del-Favero J

    更新日期:2010-11-01 00:00:00

  • Novel CASK mutations in cases with syndromic microcephaly.

    abstract::Mutations in CASK cause a wide spectrum of phenotypes in humans ranging from mild X-linked intellectual disability to a severe microcephaly (MC) and pontocerebellar hypoplasia syndrome. Nevertheless, predicting pathogenicity and phenotypic consequences of novel CASK mutations through the exclusive consideration of gen...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Cristofoli F,Devriendt K,Davis EE,Van Esch H,Vermeesch JR

    更新日期:2018-07-01 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 genomic copy number changes in patients with idiopathic mental retardation by high-resolution X-array-CGH: important role for increased gene dosage of XLMR genes.

    abstract::A tiling X-chromosome-specific genomic array with a theoretical resolution of 80 kb was developed to screen patients with idiopathic mental retardation (MR) for submicroscopic copy number differences. Four patients with aberrations previously detected at lower resolution were first analyzed. This facilitated delineati...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Froyen G,Van Esch H,Bauters M,Hollanders K,Frints SG,Vermeesch JR,Devriendt K,Fryns JP,Marynen P

    更新日期:2007-10-01 00:00:00

  • TCIRG1-dependent recessive osteopetrosis: mutation analysis, functional identification of the splicing defects, and in vitro rescue by U1 snRNA.

    abstract::Human malignant infantile osteopetrosis (arOP) is a genetically heterogeneous autosomal recessive disorder of bone metabolism. The TCIRG1 gene, encoding the a3 subunit of the vacuolar proton pump, which mediates the acidification of the bone/osteoclast interface, is responsible for more than one-half of the arOP patie...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Susani L,Pangrazio A,Sobacchi C,Taranta A,Mortier G,Savarirayan R,Villa A,Orchard P,Vezzoni P,Albertini A,Frattini A,Pagani F

    更新日期:2004-09-01 00:00:00

  • Assessment of predicted enzymatic activity of α-N-acetylglucosaminidase variants of unknown significance for CAGI 2016.

    abstract::The NAGLU challenge of the fourth edition of the Critical Assessment of Genome Interpretation experiment (CAGI4) in 2016, invited participants to predict the impact of variants of unknown significance (VUS) on the enzymatic activity of the lysosomal hydrolase α-N-acetylglucosaminidase (NAGLU). Deficiencies in NAGLU ac...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Clark WT,Kasak L,Bakolitsa C,Hu Z,Andreoletti G,Babbi G,Bromberg Y,Casadio R,Dunbrack R,Folkman L,Ford CT,Jones D,Katsonis P,Kundu K,Lichtarge O,Martelli PL,Mooney SD,Nodzak C,Pal LR,Radivojac P,Savojardo C,Shi

    更新日期:2019-09-01 00:00:00

  • Homologous loci DXYS156X and DXYS156Y contain a polymorphic pentanucleotide repeat (TAAAA)n and map to human X and Y chromosomes.

    abstract::We report the isolation and characterization of a polymorphic pentanucleotide repeat (TAAAA)n, which was mapped to human chromosomes X and Y (loci DXYS156X and DXYS156Y) by PCR amplification of DNA from a monochromosomal somatic cell hybrid panel (NIGMS panel 2). The (TAAAA)n repeat of loci DXYS156 occurs within a hum...

    journal_title:Human mutation

    pub_type: 杂志文章


    authors: Chen H,Lowther W,Avramopoulos D,Antonarakis SE

    更新日期:1994-01-01 00:00:00

  • Multiple LRRK2 variants modulate risk of Parkinson disease: a Chinese multicenter study.

    abstract::We and others found two polymorphic LRRK2 (leucine-rich repeat kinase 2) variants (rs34778348:G>A; p.G2385R and rs33949390:G>C; p.R1628P) associated with Parkinson disease (PD) among Chinese patients, but the common worldwide rs34637584:G>A; p.G2019S mutation, was absent. Focusing exclusively on Han Chinese, we first ...

    journal_title:Human mutation

    pub_type: 杂志文章,多中心研究


    authors: Tan EK,Peng R,Teo YY,Tan LC,Angeles D,Ho P,Chen ML,Lin CH,Mao XY,Chang XL,Prakash KM,Liu JJ,Au WL,Le WD,Jankovic J,Burgunder JM,Zhao Y,Wu RM

    更新日期:2010-05-01 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