当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > P4HA1 mutations cause a unique congenital disorder of connective tissue involving tendon, bone, muscle and the eye.

P4HA1 mutations cause a unique congenital disorder of connective tissue involving tendon, bone, muscle and the eye.

Abstract：

:Collagen prolyl 4-hydroxylases (C-P4Hs) play a central role in the formation and stabilization of the triple helical domain of collagens. P4HA1 encodes the catalytic α(I) subunit of the main C-P4H isoenzyme (C-P4H-I). We now report human bi-allelic P4HA1 mutations in a family with a congenital-onset disorder of connective tissue, manifesting as early-onset joint hypermobility, joint contractures, muscle weakness and bone dysplasia as well as high myopia, with evidence of clinical improvement of motor function over time in the surviving patient. Similar to P4ha1 null mice, which die prenatally, the muscle tissue from P1 and P2 was found to have reduced collagen IV immunoreactivity at the muscle basement membrane. Patients were compound heterozygous for frameshift and splice site mutations leading to reduced, but not absent, P4HA1 protein level and C-P4H activity in dermal fibroblasts compared to age-matched control samples. Differential scanning calorimetry revealed reduced thermal stability of collagen in patient-derived dermal fibroblasts versus age-matched control samples. Mutations affecting the family of C-P4Hs, and in particular C-P4H-I, should be considered in patients presenting with congenital connective tissue/myopathy overlap disorders with joint hypermobility, contractures, mild skeletal dysplasia and high myopia.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Zou Y,Donkervoort S,Salo AM,Foley AR,Barnes AM,Hu Y,Makareeva E,Leach ME,Mohassel P,Dastgir J,Deardorff MA,Cohn RD,DiNonno WO,Malfait F,Lek M,Leikin S,Marini JC,Myllyharju J,Bönnemann CG

doi

10.1093/hmg/ddx110

subject

Has Abstract

pub_date

2017-06-15 00:00:00

pages

2207-2217

issue

12

eissn

0964-6906

issn

1460-2083

pii

3611511

journal_volume

26

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • Mice with an isoform-ablating Mecp2 exon 1 mutation recapitulate the neurologic deficits of Rett syndrome.

    abstract：:Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT OMIM 312750). Alternative inclusion of MECP2/Mecp2 exon 1 with exons 3 and 4 encodes MeCP2-e1 or MeCP2-e2 protein isoforms with unique amino termini. While most MECP2 mutations are located in exons 3 and 4 thus affecting both isoforms, MECP2 e...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt640

    authors： Yasui DH,Gonzales ML,Aflatooni JO,Crary FK,Hu DJ,Gavino BJ,Golub MS,Vincent JB,Carolyn Schanen N,Olson CO,Rastegar M,Lasalle JM

    更新日期：2014-05-01 00:00:00

  • Low-pass whole genome bisulfite sequencing of neonatal dried blood spots identifies a role for RUNX1 in Down syndrome DNA methylation profiles.

    abstract：:Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddaa218

    authors： Laufer BI,Hwang H,Jianu JM,Mordaunt CE,Korf IF,Hertz-Picciotto I,LaSalle JM

    更新日期：2021-01-06 00:00:00

  • Structural characterization of the FKHR gene and its rearrangement in alveolar rhabdomyosarcoma.

    abstract：:The FKHR gene, which contains a forkhead DNA-binding motif, is fused to either PAX3 or PAX7 by the t(2;13) or t(1;13) translocation in alveolar rhabdomyosarcoma,respectively. These tumors express chimeric transcripts encoding the N-terminal portion of either PAX protein fused to the C-terminal portion of FKHR. To unde...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.12.2355

    authors： Davis RJ,Bennicelli JL,Macina RA,Nycum LM,Biegel JA,Barr FG

    更新日期：1995-12-01 00:00:00

  • Epigallocatechin-3-gallate and related phenol compounds redirect the amyloidogenic aggregation pathway of ataxin-3 towards non-toxic aggregates and prevent toxicity in neural cells and Caenorhabditis elegans animal model.

    abstract：:The protein ataxin-3 (ATX3) triggers an amyloid-related neurodegenerative disease when its polyglutamine stretch is expanded beyond a critical threshold. We formerly demonstrated that the polyphenol epigallocatechin-3-gallate (EGCG) could redirect amyloid aggregation of a full-length, expanded ATX3 (ATX3-Q55) towards ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx211

    authors： Visentin C,Pellistri F,Natalello A,Vertemara J,Bonanomi M,Gatta E,Penco A,Relini A,De Gioia L,Airoldi C,Regonesi ME,Tortora P

    更新日期：2017-09-01 00:00:00

  • Specific correction of a splice defect in brain by nutritional supplementation.

    abstract：:Recent studies emphasize the importance of mRNA splicing in human genetic disease, as 20-30% of all disease-causing mutations are predicted to result in mRNA splicing defects. The plasticity of the mRNA splicing reaction has made these mutations attractive candidates for the development of therapeutics. Familial dysau...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr333

    authors： Shetty RS,Gallagher CS,Chen YT,Hims MM,Mull J,Leyne M,Pickel J,Kwok D,Slaugenhaupt SA

    更新日期：2011-11-01 00:00:00

  • Quantification of tRNA3243(Leu) point mutation of mitochondrial DNA in MELAS patients and its effects on mitochondrial transcription.

    abstract：:The MELAS syndrome is a mitochondrial encephalomyopathy associated with a point mutation at nucleotide 3243 of mitochondrial DNA (mtDNA). The same mutation has also been found in patients with maternally inherited diabetes mellitus. The mutation occurs within a sequence needed for termination of mitochondrial transcri...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/2.5.525

    authors： Suomalainen A,Majander A,Pihko H,Peltonen L,Syvänen AC

    更新日期：1993-05-01 00:00:00

  • Argonaute-2-dependent rescue of a Drosophila model of FXTAS by FRAXE premutation repeat.

    abstract：:Fragile X Syndrome is the most common form of hereditary mental retardation. It is caused by a large expansion of the CGG trinucleotide repeat (>200 repeats) in the 5'-untranslated region (UTR) of the FMR1 gene that leads to silencing of its transcript. Individuals with CGG repeat expansions approximately between 60 a...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm186

    authors： Sofola OA,Jin P,Botas J,Nelson DL

    更新日期：2007-10-01 00:00:00

  • Combining P301L and S320F tau variants produces a novel accelerated model of tauopathy.

    abstract：:Understanding the biological functions of tau variants can illuminate differential etiologies of Alzheimer's disease (AD) and primary tauopathies. Though the end-stage neuropathological attributes of AD and primary tauopathies are similar, the etiology and behavioral outcomes of these diseases follow unique and diverg...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddz151

    authors： Koller EJ,Gonzalez De La Cruz E,Machula T,Ibanez KR,Lin WL,Williams T,Riffe CJ,Ryu D,Strang KH,Liu X,Janus C,Golde TE,Dickson D,Giasson BI,Chakrabarty P

    更新日期：2019-10-01 00:00:00

  • Defective nephrin trafficking caused by missense mutations in the NPHS1 gene: insight into the mechanisms of congenital nephrotic syndrome.

    abstract：:Congenital nephrotic syndrome of the Finnish type (CNF or NPHS1) is an autosomal recessive kidney disorder resulting in severe proteinurea and renal dysfunction. Although the disease occurs predominantly in the Finnish population, many cases in other populations have also been reported. The disease gene (NPHS1) encode...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.23.2637

    authors： Liu L,Doné SC,Khoshnoodi J,Bertorello A,Wartiovaara J,Berggren PO,Tryggvason K

    更新日期：2001-11-01 00:00:00

  • A missense mutation in ASRGL1 is involved in causing autosomal recessive retinal degeneration.

    abstract：:Inherited retinal dystrophies are a group of genetically heterogeneous conditions with broad phenotypic heterogeneity. We analyzed a large five-generation pedigree with early-onset recessive retinal degeneration to identify the causative mutation. Linkage analysis and homozygosity mapping combined with exome sequencin...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw113

    authors： Biswas P,Chavali VR,Agnello G,Stone E,Chakarova C,Duncan JL,Kannabiran C,Homsher M,Bhattacharya SS,Naeem MA,Kimchi A,Sharon D,Iwata T,Riazuddin S,Reddy GB,Hejtmancik JF,Georgiou G,Riazuddin SA,Ayyagari R

    更新日期：2016-06-15 00:00:00

  • Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A (calpainopathy).

    abstract：:Limb girdle muscular dystrophy 2A is due to loss-of-function mutations in the Calpain 3 (CAPN3) gene. Our previous data suggest that CAPN3 helps to maintain the integrity of the triad complex in skeletal muscle. In Capn3 knock-out mice (C3KO), Ca2+ release and Ca2+/calmodulin kinase II (CaMKII) signaling are attenuate...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw086

    authors： Kramerova I,Ermolova N,Eskin A,Hevener A,Quehenberger O,Armando AM,Haller R,Romain N,Nelson SF,Spencer MJ

    更新日期：2016-06-01 00:00:00

  • Tsc/mTORC1 signaling in oocytes governs the quiescence and activation of primordial follicles.

    abstract：:To maintain the female reproductive lifespan, the majority of ovarian primordial follicles are preserved in a quiescent state in order to provide ova for later reproductive life. However, the molecular mechanism that maintains the long quiescence of primordial follicles is poorly understood. Here we provide genetic ev...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp483

    authors： Adhikari D,Zheng W,Shen Y,Gorre N,Hämäläinen T,Cooney AJ,Huhtaniemi I,Lan ZJ,Liu K

    更新日期：2010-02-01 00:00:00

  • Population structure of Han Chinese in the modern Taiwanese population based on 10,000 participants in the Taiwan Biobank project.

    abstract：:The Taiwan Biobank (TWB) aims to build a nationwide research database that integrates genomic/epigenomic profiles, lifestyle patterns, dietary habits, environmental exposure history and long-term health outcomes of 300,000 residents of Taiwan. We describe here an investigation of the population structure of Han Chines...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw346

    authors： Chen CH,Yang JH,Chiang CWK,Hsiung CN,Wu PE,Chang LC,Chu HW,Chang J,Song IW,Yang SL,Chen YT,Liu FT,Shen CY

    更新日期：2016-12-15 00:00:00

  • Evidence of susceptibility loci on 4q32 and 16p12 for bipolar disorder.

    abstract：:We performed a genome-wide scan for susceptibility loci in bipolar disorder in a study sample colleted from the isolated Finnish population, consisting of 41 families with at least two affected siblings. We identified one distinct locus on 16p12 providing significant evidence for linkage in two-point analysis (Z(max)=...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg199

    authors： Ekholm JM,Kieseppä T,Hiekkalinna T,Partonen T,Paunio T,Perola M,Ekelund J,Lönnqvist J,Pekkarinen-Ijäs P,Peltonen L

    更新日期：2003-08-01 00:00:00

  • The genetic and metabolic signature of oncocytic transformation implicates HIF1alpha destabilization.

    abstract：:We previously showed that disruptive complex I mutations in mitochondrial DNA are the main genetic hallmark of oncocytic tumors of the thyroid and kidney. We here report a high frequency of homoplasmic disruptive mutations in a large panel of oncocytic pituitary and head-and-neck tumors. The presence of such mutations...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp566

    authors： Porcelli AM,Ghelli A,Ceccarelli C,Lang M,Cenacchi G,Capristo M,Pennisi LF,Morra I,Ciccarelli E,Melcarne A,Bartoletti-Stella A,Salfi N,Tallini G,Martinuzzi A,Carelli V,Attimonelli M,Rugolo M,Romeo G,Gasparre G

    更新日期：2010-03-15 00:00:00

  • Neuronal pentraxin 1 depletion delays neurodegeneration and extends life in Sandhoff disease mice.

    abstract：:GM2 gangliosidoses are a group of lysosomal storage disorders which include Sandhoff disease and Tay-Sachs disease. Dysregulation of glutamate receptors has been recently postulated in the pathology of Sandhoff disease. Glutamate receptor association with neuronal pentraxins 1 and 2, and the neuronal pentraxin recepto...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw422

    authors： Hooper AWM,Alamilla JF,Venier RE,Gillespie DC,Igdoura SA

    更新日期：2017-02-15 00:00:00

  • Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus.

    abstract：:IGF2 loss of imprinting (LOI) is fairly prevalent and implicated in the pathogenesis of human cancer and developmental disease; however, the causes of this phenomenon are largely unknown. We determined whether the post-weaning diet of mice affects allelic expression and CpG methylation of Igf2. C57BL/6JxCast/EiJ F1 hy...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi484

    authors： Waterland RA,Lin JR,Smith CA,Jirtle RL

    更新日期：2006-03-01 00:00:00

  • Disc1 regulates granule cell migration in the developing hippocampus.

    abstract：:Schizophrenia is a severely debilitating psychiatric disease that is hypothesized to have its roots in neurodevelopment. Although the precise neuropathology underlying schizophrenia has remained elusive, there are consistent reports of abnormalities in several brain areas. Chief among these is the hippocampus, an area...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp266

    authors： Meyer KD,Morris JA

    更新日期：2009-09-01 00:00:00

  • Rab11 rescues synaptic dysfunction and behavioural deficits in a Drosophila model of Huntington's disease.

    abstract：:Synapse abnormalities in Huntington's disease (HD) patients can precede clinical diagnosis and neuron loss by decades. The polyglutamine expansion in the huntingtin (htt) protein that underlies this disorder leads to perturbations in many cellular pathways, including the disruption of Rab11-dependent endosomal recycli...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds117

    authors： Steinert JR,Campesan S,Richards P,Kyriacou CP,Forsythe ID,Giorgini F

    更新日期：2012-07-01 00:00:00

  • HSC20 interacts with frataxin and is involved in iron-sulfur cluster biogenesis and iron homeostasis.

    abstract：:Friedreich's ataxia is a neurodegenerative disorder caused by mutations in the frataxin gene that produces a predominantly mitochondrial protein whose primary function appears to be mitochondrial iron-sulfur cluster (ISC) biosynthesis. Previously we demonstrated that frataxin interacts with multiple components of the ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr582

    authors： Shan Y,Cortopassi G

    更新日期：2012-04-01 00:00:00

  • Multifaceted Hoxa13 function in urogenital development underlies the Hand-Foot-Genital Syndrome.

    abstract：:Hand-Foot-Genital syndrome is a rare condition caused by mutations in the HOXA13 gene and characterized by limb malformations and urogenital defects. While the role of Hoxa13 in limb development has been extensively studied, its function during the development of the urogenital system remains elusive mostly due to the...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddz013

    authors： Roux M,Bouchard M,Kmita M

    更新日期：2019-05-15 00:00:00

  • Genomic structure and parent-of-origin-specific methylation of Peg1.

    abstract：:We previously identified Peg1/Mest as a novel paternally expressed gene in the developing mouse embryo. The human PEG1 gene was recently assigned to 7q32 and shown to be imprinted and paternally expressed. Therefore, PEG1 deficiency could participate in the aetiology of pre- and post-natal growth retardation associate...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/6.11.1907

    authors： Lefebvre L,Viville S,Barton SC,Ishino F,Surani MA

    更新日期：1997-10-01 00:00:00

  • Functional characterization of the AFF (AF4/FMR2) family of RNA-binding proteins: insights into the molecular pathology of FRAXE intellectual disability.

    abstract：:The AFF (AF4/FMR2) family of genes includes four members: AFF1/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. AFF2/FMR2 is silenced in FRAXE intellectual disability, while the other three members have been reported to form fusion genes as a consequence of chromosome translocations with the myeloid/lymphoid or mixed lineag...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr069

    authors： Melko M,Douguet D,Bensaid M,Zongaro S,Verheggen C,Gecz J,Bardoni B

    更新日期：2011-05-15 00:00:00

  • Progressive axonal transport and synaptic protein changes correlate with behavioral and neuropathological abnormalities in the heterozygous Q175 KI mouse model of Huntington's disease.

    abstract：:A long-term goal of modeling Huntington's disease (HD) is to recapitulate the cardinal features of the disease in mice that express both mutant and wild-type (WT) huntingtin (Htt), as HD commonly manifests as a heterozygous condition in humans, and loss of WT Htt is associated with loss-of-function. In a new heterozyg...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu166

    authors： Smith GA,Rocha EM,McLean JR,Hayes MA,Izen SC,Isacson O,Hallett PJ

    更新日期：2014-09-01 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

  • Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model.

    abstract：:Spinocerebellar ataxia type 1 (SCA1) is one of nine dominantly inherited neurodegenerative diseases caused by polyglutamine tract expansion. In SCA1, the expanded polyglutamine tract is in the ataxin-1 (ATXN1) protein. ATXN1 is part of an in vivo complex with retinoid acid receptor-related orphan receptor alpha (Rora)...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr108

    authors： Gehrking KM,Andresen JM,Duvick L,Lough J,Zoghbi HY,Orr HT

    更新日期：2011-06-01 00:00:00

  • Zebrafish cul4a, but not cul4b, modulates cardiac and forelimb development by upregulating tbx5a expression.

    abstract：:CUL4A and CUL4B are closely related cullin family members and can each assemble a Cullin-RING E3 ligase complex (CRL) and participate in a variety of biological processes. While the CRLs formed by the two cullin members may have common targets, the two appeared to have very different consequences when mutated or disru...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddu503

    authors： Zhao X,Jiang B,Hu H,Mao F,Mi J,Li Z,Liu Q,Shao C,Gong Y

    更新日期：2015-02-01 00:00:00

  • Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity.

    abstract：:Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine expansion in the disease protein, huntingtin. In HD patients and transgenic mice, the affected neurons form characteristic ubiquitin-positive nuclear inclusions (NIs). We have established ecdysone-inducible stable mou...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.13.2009

    authors： Jana NR,Tanaka M,Wang Gh,Nukina N

    更新日期：2000-08-12 00:00:00

  • NAFLD risk alleles in PNPLA3, TM6SF2, GCKR and LYPLAL1 show divergent metabolic effects.

    abstract：:Fatty liver has been associated with unfavourable metabolic changes in circulation. To provide insights in fatty liver-related metabolic deviations, we compared metabolic association profile of fatty liver versus metabolic association profiles of genotypes increasing the risk of non-alcoholic fatty liver disease (NAFL...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy124

    authors： Sliz E,Sebert S,Würtz P,Kangas AJ,Soininen P,Lehtimäki T,Kähönen M,Viikari J,Männikkö M,Ala-Korpela M,Raitakari OT,Kettunen J

    更新日期：2018-06-15 00:00:00

  • Uner Tan syndrome caused by a homozygous TUBB2B mutation affecting microtubule stability.

    abstract：:The integrity and dynamic properties of the microtubule cytoskeleton are indispensable for the development of the mammalian brain. Consequently, mutations in the genes that encode the structural component (the α/β-tubulin heterodimer) can give rise to severe, sporadic neurodevelopmental disorders. These are commonly r...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw383

    authors： Breuss MW,Nguyen T,Srivatsan A,Leca I,Tian G,Fritz T,Hansen AH,Musaev D,McEvoy-Venneri J,James KN,Rosti RO,Scott E,Tan U,Kolodner RD,Cowan NJ,Keays DA,Gleeson JG

    更新日期：2017-01-15 00:00:00