当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > Mild Nijmegen breakage syndrome phenotype due to alternative splicing.

Mild Nijmegen breakage syndrome phenotype due to alternative splicing.

Abstract：

:Hypomorphic mutations of the NBS1 gene are responsible for Nijmegen breakage syndrome (NBS), characterized by microcephaly, chromosomal instability, radiosensitivity, immunodeficiency and high cancer predisposition. Over 90% of NBS patients are homozygous for the 657Delta5 mutation and are of Slavic origin; however, 10 further truncating mutations have been identified in patients of other ethnic origin. Partially functional proteins produced by alternative initiation of translation, and possibly diminishing the severity of the NBS phenotype, have been described for several NBS1 mutations. Here, we report a 53-year-old NBS patient, homozygous for the NBS1 mutation, 742insGG, in exon 7 and who presents with a particularly mild phenotype. In an attempt to find a potential molecular explanation for the mild phenotype observed, we carried out a conventional semi-quantitative and quantitative RT-PCR analyses which revealed two transcripts of almost equal amounts in the patient and her parents--the expected full-length transcript carrying the 742insGG mutation and a second transcript with deleted exons 6 and 7. The transcript was also observed in controls and other NBS patients, however, at quantities more than 100-fold lower than that in the patient described here. Because the skipping of exons 6 and 7 results in an internal in-frame deletion, which eliminates the truncating GG-insertion, we propose that this transcript may code for a partially functional protein of approximately 70 kDa that could be responsible for the unusually mild NBS phenotype observed in this patient. Indeed, complementation analysis of null-mutant mouse cells indicates that the alternatively spliced mRNA codes for a protein with significant functional capacity.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Varon R,Dutrannoy V,Weikert G,Tanzarella C,Antoccia A,Stöckl L,Spadoni E,Krüger LA,di Masi A,Sperling K,Digweed M,Maraschio P

doi

10.1093/hmg/ddi482

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

679-89

issue

5

eissn

0964-6906

issn

1460-2083

pii

ddi482

journal_volume

15

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • Structural features of normal and mutant human lysosomal glycoside hydrolases deduced from bioinformatics analysis.

    abstract：:Lysosomal storage diseases are due to inherited deficiencies in various enzymes involved in basic metabolic processes. As with other genetic diseases, accurate structure data for these enzymatic proteins should help in better understanding the molecular effects of mutations identified in patients with the correspondin...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/9.6.967

    authors： Durand P,Fabrega S,Henrissat B,Mornon JP,Lehn P

    更新日期：2000-04-12 00:00:00

  • Copy number variations on chromosome 12q14 in patients with normal tension glaucoma.

    abstract：:We report identification of a novel genetic locus (GLC1P) for normal tension glaucoma (NTG) on chromosome 12q14 using linkage studies of an African-American pedigree (maximum non-parametric linkage score = 19.7, max LOD score = 2.7). Subsequent comparative genomic hybridization and quantitative polymerase chain reacti...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr123

    authors： Fingert JH,Robin AL,Stone JL,Roos BR,Davis LK,Scheetz TE,Bennett SR,Wassink TH,Kwon YH,Alward WL,Mullins RF,Sheffield VC,Stone EM

    更新日期：2011-06-15 00:00:00

  • Chromosome-specific accumulation of aneuploidy in the aging mouse brain.

    abstract：:Chromosomal aneuploidy, the gain or loss of whole chromosomes, is a hallmark of pathological conditions and a causal factor of birth defects and cancer. A number of studies indicate that aneuploid cells are present at a high frequency in the brain of mice and humans, suggesting that mosaic aneuploidies are compatible ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds375

    authors： Faggioli F,Wang T,Vijg J,Montagna C

    更新日期：2012-12-15 00:00:00

  • Mutations in Emery-Dreifuss muscular dystrophy and their effects on emerin protein expression.

    abstract：:Seventeen families with Emery-Dreifuss muscular dystrophy (EDMD) have been studied both by DNA sequencing and by emerin protein expression. Fourteen had mutations in the X-linked emerin gene, while three showed evidence of autosomal inheritance. Twelve of the 14 emerin mutations caused early termination of translation...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/7.5.855

    authors： Manilal S,Recan D,Sewry CA,Hoeltzenbein M,Llense S,Leturcq F,Deburgrave N,Barbot J,Man N,Muntoni F,Wehnert M,Kaplan J,Morris GE

    更新日期：1998-05-01 00:00:00

  • Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci.

    abstract：:Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically dive...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw358

    authors： Zubair N,Graff M,Luis Ambite J,Bush WS,Kichaev G,Lu Y,Manichaikul A,Sheu WH,Absher D,Assimes TL,Bielinski SJ,Bottinger EP,Buzkova P,Chuang LM,Chung RH,Cochran B,Dumitrescu L,Gottesman O,Haessler JW,Haiman C,Heiss

    更新日期：2016-12-15 00:00:00

  • SOX10 regulates an alternative promoter at the Charcot-Marie-Tooth disease locus MTMR2.

    abstract：:Schwann cells are the myelinating glia of the peripheral nervous system and dysfunction of these cells causes motor and sensory peripheral neuropathy. The transcription factor SOX10 is critical for Schwann cell development and maintenance, and many SOX10 target genes encode proteins required for Schwann cell function....

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw233

    authors： Fogarty EA,Brewer MH,Rodriguez-Molina JF,Law WD,Ma KH,Steinberg NM,Svaren J,Antonellis A

    更新日期：2016-09-15 00:00:00

  • Confirmation of the DRB1-DQB1 loci as the major component of IDDM1 in the isolated founder population of Sardinia.

    abstract：:There is considerable uncertainty and debate concerning the application of linkage disequilibrium (LD) mapping in common multifactorial diseases, including the choice of population and the density of the marker map. Previously, it has been shown that, in the large cosmopolitan population of the UK, the established typ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.20.2967

    authors： Zavattari P,Lampis R,Mulargia A,Loddo M,Angius E,Todd JA,Cucca F

    更新日期：2000-12-12 00:00:00

  • Regulation of retinal progenitor expansion by Frizzled receptors: implications for microphthalmia and retinal coloboma.

    abstract：:Nineteen Wnt ligands and 10 Frizzled (Fz) receptors mediate multiple distinct cellular events during neuronal development. However, their precise roles in cell-type specification and organogenesis are poorly delineated because of overlapping functions and expression profiles. Here, we have explored the role of two clo...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr616

    authors： Liu C,Bakeri H,Li T,Swaroop A

    更新日期：2012-04-15 00:00:00

  • A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol.

    abstract：:Single nucleotide polymorphisms (SNPs) that alter exon splicing efficiency are an emerging class of functional genetic variants. Since mutations in low-density lipoprotein receptor (LDLR) are a primary cause of familial hypercholesterolemia, we evaluated whether LDLR SNPs may alter splicing efficiency and cholesterol ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm124

    authors： Zhu H,Tucker HM,Grear KE,Simpson JF,Manning AK,Cupples LA,Estus S

    更新日期：2007-07-15 00:00:00

  • Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways.

    abstract：:Autism is a heterogeneous condition that is likely to result from the combined effects of multiple genetic factors interacting with environmental factors. Given its complexity, the study of autism associated with Mendelian single gene disorders or known chromosomal etiologies provides an important perspective. We used...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm116

    authors： Nishimura Y,Martin CL,Vazquez-Lopez A,Spence SJ,Alvarez-Retuerto AI,Sigman M,Steindler C,Pellegrini S,Schanen NC,Warren ST,Geschwind DH

    更新日期：2007-07-15 00:00:00

  • Progress in defining the molecular basis of type 2 diabetes mellitus through susceptibility-gene identification.

    abstract：:The rapid increase in the prevalence of type 2 diabetes (T2D) represents a major challenge for health care delivery worldwide. Identification of genes influencing individual susceptibility to disease offers a route to better understanding of the molecular mechanisms underlying pathogenesis, a necessary prerequisite fo...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/ddh057

    authors： McCarthy MI

    更新日期：2004-04-01 00:00:00

  • Systems-level analysis of human aging genes shed new light on mechanisms of aging.

    abstract：:Although studies over the last decades have firmly connected a number of genes and molecular pathways to aging, the aging process as a whole still remains poorly understood. To gain novel insights into the mechanisms underlying aging, instead of considering aging genes individually, we studied their characteristics at...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw145

    authors： Zhang Q,Nogales-Cadenas R,Lin JR,Zhang W,Cai Y,Vijg J,Zhang ZD

    更新日期：2016-07-15 00:00:00

  • Identification of cis-regulatory variation influencing protein abundance levels in human plasma.

    abstract：:Proteins are central to almost all cellular processes, and dysregulation of expression and function is associated with a range of disorders. A number of studies in human have recently shown that genetic factors significantly contribute gene expression variation. In contrast, very little is known about the genetic basi...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds186

    authors： Lourdusamy A,Newhouse S,Lunnon K,Proitsi P,Powell J,Hodges A,Nelson SK,Stewart A,Williams S,Kloszewska I,Mecocci P,Soininen H,Tsolaki M,Vellas B,Lovestone S,AddNeuroMed Consortium.,Dobson R,Alzheimer's Disease Neuroimag

    更新日期：2012-08-15 00:00:00

  • Ildr1b is essential for semicircular canal development, migration of the posterior lateral line primordium and hearing ability in zebrafish: implications for a role in the recessive hearing impairment DFNB42.

    abstract：:Immunoglobulin-like domain containing receptor 1 (ILDR1) is a poorly characterized gene that was first identified in lymphoma cells. Recently, ILDR1 has been found to be responsible for autosomal recessive hearing impairment DFNB42. Patients with ILDR1 mutations cause bilateral non-progressive moderate-to-profound sen...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu340

    authors： Sang Q,Zhang J,Feng R,Wang X,Li Q,Zhao X,Xing Q,Chen W,Du J,Sun S,Chai R,Liu D,Jin L,He L,Li H,Wang L

    更新日期：2014-12-01 00:00:00

  • Loss of Tbx1 induces bone phenotypes similar to cleidocranial dysplasia.

    abstract：:T-box transcription factor, TBX1, is the major candidate gene for 22q11.2 deletion syndrome (DiGeorge/ Velo-cardio-facial syndrome) characterized by facial defects, thymus hypoplasia, cardiovascular anomalies and cleft palates. Here, we report that the loss of Tbx1 in mouse (Tbx1(-/-)) results in skeletal abnormalitie...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu458

    authors： Funato N,Nakamura M,Richardson JA,Srivastava D,Yanagisawa H

    更新日期：2015-01-15 00:00:00

  • Different mechanisms cause imprinting defects at the IGF2/H19 locus in Beckwith-Wiedemann syndrome and Wilms' tumour.

    abstract：:The parent of origin-dependent expression of the IGF2 and H19 genes is controlled by the imprinting centre 1 (IC1) consisting in a methylation-sensitive chromatin insulator. Deletions removing part of IC1 have been found in patients affected by the overgrowth- and tumour-associated Beckwith-Wiedemann syndrome (BWS). T...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddn031

    authors： Cerrato F,Sparago A,Verde G,De Crescenzo A,Citro V,Cubellis MV,Rinaldi MM,Boccuto L,Neri G,Magnani C,D'Angelo P,Collini P,Perotti D,Sebastio G,Maher ER,Riccio A

    更新日期：2008-05-15 00:00:00

  • Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region.

    abstract：:Deletions of the 22q11.2 region distal to the 22q11.21 microdeletion syndrome region have recently been described in individuals with mental retardation and congenital anomalies. Because these deletions are mediated by low-copy repeats (LCRs), located distal to the 22q11.21 DiGeorge/velocardiofacial microdeletion regi...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp042

    authors： Coppinger J,McDonald-McGinn D,Zackai E,Shane K,Atkin JF,Asamoah A,Leland R,Weaver DD,Lansky-Shafer S,Schmidt K,Feldman H,Cohen W,Phalin J,Powell B,Ballif BC,Theisen A,Geiger E,Haldeman-Englert C,Shaikh TH,Saitta S,

    更新日期：2009-04-15 00:00:00

  • Inherited neurodegenerative diseases: the one-hit model of neurodegeneration.

    abstract：:The clinical manifestations of inherited neurodegenerative diseases are often delayed for periods from years to decades. This observation has led to the idea that, in these disorders, neurons die from cumulative damage. A critical prediction of the cumulative damage hypothesis is that the probability of neuronal death...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/10.20.2269

    authors： Clarke G,Lumsden CJ,McInnes RR

    更新日期：2001-10-01 00:00:00

  • Ciliopathy-associated mutations of IFT122 impair ciliary protein trafficking but not ciliogenesis.

    abstract：:The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. Mutations in the genes encoding the six subunits of the IFT-A complex (IFT43, IFT121, IFT122, IFT139, IFT140, and IFT144) are known to cause skeletal ciliopathies, including cranioectodermal dysp...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx421

    authors： Takahara M,Katoh Y,Nakamura K,Hirano T,Sugawa M,Tsurumi Y,Nakayama K

    更新日期：2018-02-01 00:00:00

  • Fragile sites and human disease.

    abstract：:A relationship between fragile sites, specific genomic regions visible as gaps or breaks on cultivated chromosomes, and human disease has been proposed many years ago. Evidence for a role of the ubiquitously expressed common fragile sites characterized by peculiar genome architecture in cancer has been accumulated ove...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/ddm136

    authors： Debacker K,Kooy RF

    更新日期：2007-10-15 00:00:00

  • The PINK1/Parkin pathway regulates mitochondrial dynamics and function in mammalian hippocampal and dopaminergic neurons.

    abstract：:PTEN-induced putative kinase 1 (PINK1) and Parkin act in a common pathway to regulate mitochondrial dynamics, the involvement of which in the pathogenesis of Parkinson's disease (PD) is increasingly being appreciated. However, how the PINK1/Parkin pathway influences mitochondrial function is not well understood, and t...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr235

    authors： Yu W,Sun Y,Guo S,Lu B

    更新日期：2011-08-15 00:00:00

  • Advances in gene therapy for cystic fibrosis lung disease.

    abstract：:Cystic fibrosis (CF) is a multiorgan recessive genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Gene therapy efforts have focused on treating the lung, since it manifests the most significant life-threatening disease. Over two decades have past since the first...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/ddz139

    authors： Yan Z,McCray PB Jr,Engelhardt JF

    更新日期：2019-10-01 00:00:00

  • Recessively inherited L-DOPA-responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene.

    abstract：:Tyrosine hydroxylase (TH) catalyzes the conversion of L-tyrosine to L-dihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of dopamine. Recently, we described a point mutation in hTH (Q381K) in a family of two siblings suffering from progressive L-DOPA-responsive dystonia (DRD), representing the...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.7.1209

    authors： Knappskog PM,Flatmark T,Mallet J,Lüdecke B,Bartholomé K

    更新日期：1995-07-01 00:00:00

  • Glutaredoxin deficiency exacerbates neurodegeneration in C. elegans models of Parkinson's disease.

    abstract：:Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic neurons. Although the etiology of PD remains incompletely understood, oxidative stress has been implicated as an important contributor in the development of PD. Oxidative stress can lead to oxidation and functional perturbation of prot...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu542

    authors： Johnson WM,Yao C,Siedlak SL,Wang W,Zhu X,Caldwell GA,Wilson-Delfosse AL,Mieyal JJ,Chen SG

    更新日期：2015-03-01 00:00:00

  • Mapping of the familial infantile myasthenia (congenital myasthenic syndrome type Ia) gene to chromosome 17p with evidence of genetic homogeneity.

    abstract：:Familial infantile myasthenia is an autosomal recessive disorder, recently classified as congenital myasthenic syndrome type Ia. Onset of symptoms is at birth to early childhood with significant myasthenic weakness and possible respiratory distress, followed later in life by symptoms of mild to moderate myasthenia. Th...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/6.4.635

    authors： Christodoulou K,Tsingis M,Deymeer F,Serdaroglu P,Ozdemir C,Al-Shehab A,Bairactaris C,Mavromatis I,Mylonas I,Evoli A,Kyriallis K,Middleton LT

    更新日期：1997-04-01 00:00:00

  • Molecular genetic investigations identify new clinical phenotypes associated with BCS1L-related mitochondrial disease.

    abstract：:BCS1L encodes a homolog of the Saccharomyces cerevisiae bcs1 protein, which has a known role in the assembly of Complex III of the mitochondrial respiratory chain. Phenotypes reported in association with pathogenic BCS1L variants include growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis an...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddz202

    authors： Oláhová M,Ceccatelli Berti C,Collier JJ,Alston CL,Jameson E,Jones SA,Edwards N,He L,Chinnery PF,Horvath R,Goffrini P,Taylor RW,Sayer JA

    更新日期：2019-11-15 00:00:00

  • Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas.

    abstract：:Meningiomas are common nervous system tumors, whose molecular pathogenesis is poorly understood. To date, the most frequent genetic alteration detected in these tumors is loss of heterozygosity (LOH) on chromosome 22q. This finding led to the identification of the neurofibromatosis 2 (NF2) tumor suppressor gene on 22q...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.10.1495

    authors： Gutmann DH,Donahoe J,Perry A,Lemke N,Gorse K,Kittiniyom K,Rempel SA,Gutierrez JA,Newsham IF

    更新日期：2000-06-12 00:00:00

  • Myo15 function is distinct from Myo6, Myo7a and pirouette genes in development of cochlear stereocilia.

    abstract：:The unconventional myosin genes Myo15, Myo6 and Myo7a are essential for hearing in both humans and mice. Despite the expression of each gene in multiple organs, mutations result in identifiable phenotypes only in auditory or ocular sensory organs. The pirouette (pi) mouse also exhibits deafness and an inner ear pathol...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg308

    authors： Karolyi IJ,Probst FJ,Beyer L,Odeh H,Dootz G,Cha KB,Martin DM,Avraham KB,Kohrman D,Dolan DF,Raphael Y,Camper SA

    更新日期：2003-11-01 00:00:00

  • Enhanced excitation-coupled Ca(2+) entry induces nuclear translocation of NFAT and contributes to IL-6 release from myotubes from patients with central core disease.

    abstract：:Prolonged depolarization of skeletal muscle cells induces entry of extracellular calcium into muscle cells, an event referred to as excitation-coupled calcium entry. Skeletal muscle excitation-coupled calcium entry relies on the interaction between the 1,4-dihydropyridine receptor on the sarcolemma and the ryanodine r...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddq506

    authors： Treves S,Vukcevic M,Jeannet PY,Levano S,Girard T,Urwyler A,Fischer D,Voit T,Jungbluth H,Lillis S,Muntoni F,Quinlivan R,Sarkozy A,Bushby K,Zorzato F

    更新日期：2011-02-01 00:00:00

  • Polar substitutions in helix 3 of the prion protein produce transmembrane isoforms that disturb vesicle trafficking.

    abstract：:Prion diseases encompass a diverse group of neurodegenerative conditions characterized by the accumulation of misfolded prion protein (PrP) isoforms. Other conformational variants of PrP have also been proposed to contribute to neurotoxicity in prion diseases, including misfolded intermediates as well as cytosolic and...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt276

    authors： Sanchez-Garcia J,Arbelaez D,Jensen K,Rincon-Limas DE,Fernandez-Funez P

    更新日期：2013-11-01 00:00:00