共查询到20条相似文献,搜索用时 15 毫秒
1.
David A. Parry Alan J. Mighell Walid El-Sayed Roger C. Shore Ismail K. Jalili Hlne Dollfus Agnes Bloch-Zupan Roman Carlos Ian M. Carr Louise M. Downey Katharine M. Blain David C. Mansfield Mehdi Shahrabi Mansour Heidari Parissa Aref Mohsen Abbasi Michel Michaelides Anthony T. Moore Jennifer Kirkham Chris F. Inglehearn 《American journal of human genetics》2009,84(2):266-273
The combination of recessively inherited cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI) was first reported by Jalili and Smith in 1988 in a family subsequently linked to a locus on chromosome 2q11, and it has since been reported in a second small family. We have identified five further ethnically diverse families cosegregating CRD and AI. Phenotypic characterization of teeth and visual function in the published and new families reveals a consistent syndrome in all seven families, and all link or are consistent with linkage to 2q11, confirming the existence of a genetically homogenous condition that we now propose to call Jalili syndrome. Using a positional-candidate approach, we have identified mutations in the CNNM4 gene, encoding a putative metal transporter, accounting for the condition in all seven families. Nine mutations are described in all, three missense, three terminations, two large deletions, and a single base insertion. We confirmed expression of Cnnm4 in the neural retina and in ameloblasts in the developing tooth, suggesting a hitherto unknown connection between tooth biomineralization and retinal function. The identification of CNNM4 as the causative gene for Jalili syndrome, characterized by syndromic CRD with AI, has the potential to provide new insights into the roles of metal transport in visual function and biomineralization. 相似文献
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Ziv Gan-Or Naima BouslamNazha Birouk Alexandra LissoubaDaniel B. Chambers Julie VérièpeAlaura Androschuk Sandra B. LaurentDaniel Rochefort Dan SpiegelmanAlexandre Dionne-Laporte Anna SzutoMeijiang Liao Denise A. FiglewiczAhmed Bouhouche Ali BenomarMohamed Yahyaoui Reda OuazzaniGrace Yoon Nicolas DupréOksana Suchowersky Francois V. BolducJ. Alex Parker Patrick A. DionPierre Drapeau Guy A. RouleauBouchra Ouled Amar Bencheikh 《American journal of human genetics》2016,98(6):1271
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Figen Seymen Youn Jung Kim Ye Ji Lee Jenny Kang Tak-Heun Kim Hwajung Choi Mine Koruyucu Yelda Kasimoglu Elif Bahar Tuna Koray Gencay Teo Jeon Shin Hong-Keun Hyun Young-Jae Kim Sang-Hoon Lee Zang Hee Lee Hong Zhang Jan C-C. Hu James P. Simmer Eui-Sic Cho Jung-Wook Kim 《American journal of human genetics》2016,99(5):1199-1205
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Bozena Polok Pascal Escher Aude Ambresin Eliane Chouery Sylvain Bolay Isabelle Meunier Francis Nan Christian Hamel Francis L. Munier Bernard Thilo Andr Mgarban Daniel F. Schorderet 《American journal of human genetics》2009,84(2):259-265
Cone-rod dystrophies are inherited dystrophies of the retina characterized by the accumulation of deposits mainly localized to the cone-rich macular region of the eye. Dystrophy can be limited to the retina or be part of a syndrome. Unlike nonsyndromic cone-rod dystrophies, syndromic cone-rod dystrophies are genetically heterogeneous with mutations in genes encoding structural, cell-adhesion, and transporter proteins. Using a genome-wide single-nucleotide polymorphism (SNP) haplotype analysis to fine map the locus and a gene-candidate approach, we identified homozygous mutations in the ancient conserved domain protein 4 gene (CNNM4) that either generate a truncated protein or occur in highly conserved regions of the protein. Given that CNNM4 is implicated in metal ion transport, cone-rod dystrophy and amelogenesis imperfecta may originate from abnormal ion homeostasis. 相似文献
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Fleur S. van Dijk Eline H. Zwikstra Sander R. Piersma Connie R. Jimenez Alice C. Morsman Mirjam H.H. van Roij Jonathan I.M.L. Verbeke Nick J. Shaw Carole McKeown Ann Dalton Gerard Pals 《American journal of human genetics》2009,85(4):521-527
Deficiency of cartilage-associated protein (CRTAP) or prolyl 3-hydroxylase 1(P3H1) has been reported in autosomal-recessive lethal or severe osteogenesis imperfecta (OI). CRTAP, P3H1, and cyclophilin B (CyPB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the α1 chains of collagen type I. This 3-prolyl hydroxylation is decreased in patients with CRTAP and P3H1 deficiency. It was suspected that mutations in the PPIB gene encoding CyPB would also cause OI with decreased collagen 3-prolyl hydroxylation. To our knowledge we present the first two families with recessive OI caused by PPIB gene mutations. The clinical phenotype is compatible with OI Sillence type II-B/III as seen with COL1A1/2, CRTAP, and LEPRE1 mutations. The percentage of 3-hydroxylated P986 residues in patients with PPIB mutations is decreased in comparison to normal, but it is higher than in patients with CRTAP and LEPRE1 mutations. This result and the fact that CyPB is demonstrable independent of CRTAP and P3H1, along with reported decreased 3-prolyl hydroxylation due to deficiency of CRTAP lacking the catalytic hydroxylation domain and the known function of CyPB as a cis-trans isomerase, suggest that recessive OI is caused by a dysfunctional P3H1/CRTAP/CyPB complex rather than by the lack of 3-prolyl hydroxylation of a single proline residue in the α1 chains of collagen type I. 相似文献
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Anna C. Thomas Hywel WilliamsNúria Setó-Salvia Chiara BacchelliDagan Jenkins Mary O’SullivanKonstantinos Mengrelis Miho IshidaLouise Ocaka Estelle ChanudetChela James Francesco LescaiGlenn Anderson Deborah MorroghMina Ryten Andrew J. DuncanYun Jin Pai Jorge M. SaraivaFabiana Ramos Bernadette FarrenDawn Saunders Bertrand VernayPaul Gissen Anna Straatmaan-IwanowskaFrank Baas Nicholas W. WoodJoshua Hersheson Henry HouldenJane Hurst Richard ScottMaria Bitner-Glindzicz Gudrun E. MooreSérgio B. Sousa Philip Stanier 《American journal of human genetics》2015,96(6):1008-1009
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Dikla Bandah-Rozenfeld Rob W.J. Collin Eyal Banin Karlien L.M. Coene Anna M. Siemiatkowska Lina Zelinger Dirk J. Lefeber Inbar Erdinest Francesca Simonelli Ellen A.W. Blokland Caroline C.W. Klaver Raheel Qamar Sandro Banfi Dror Sharon Anneke I. den Hollander 《American journal of human genetics》2010,87(2):199-208
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases caused by progressive degeneration of the photoreceptor cells. Using autozygosity mapping, we identified two families, each with three affected siblings sharing large overlapping homozygous regions that harbored the IMPG2 gene on chromosome 3. Sequence analysis of IMPG2 in the two index cases revealed homozygous mutations cosegregating with the disease in the respective families: three affected siblings of Iraqi Jewish ancestry displayed a nonsense mutation, and a Dutch family displayed a 1.8 kb genomic deletion that removes exon 9 and results in the absence of seven amino acids in a conserved SEA domain of the IMPG2 protein. Transient transfection of COS-1 cells showed that a construct expressing the wild-type SEA domain is properly targeted to the plasma membrane, whereas the mutant lacking the seven amino acids appears to be retained in the endoplasmic reticulum. Mutation analysis in ten additional index cases that were of Dutch, Israeli, Italian, and Pakistani origin and had homozygous regions encompassing IMPG2 revealed five additional mutations; four nonsense mutations and one missense mutation affecting a highly conserved phenylalanine residue. Most patients with IMPG2 mutations showed an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. The patient with the missense mutation, however, was diagnosed with maculopathy. The IMPG2 gene encodes the interphotoreceptor matrix proteoglycan IMPG2, which is a constituent of the interphotoreceptor matrix. Our data therefore show that mutations in a structural component of the interphotoreceptor matrix can cause arRP. 相似文献
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Yun Li Esther Pohl Redouane Boulouiz Margit Schraders Gudrun Nürnberg Majida Charif Simon von Ameln Ingelore Baessmann Joris A. Veltman Peter Nürnberg Christian Kubisch Abdelhamid Barakat Bernd Wollnik 《American journal of human genetics》2010,86(3):479-137
We performed genome-wide homozygosity mapping in a large consanguineous family from Morocco and mapped the autosomal-recessive nonsyndromic hearing loss (ARNSHL) in this family to the DFNB79 locus on chromosome 9q34. By sequencing of 62 positional candidate genes of the critical region, we identified a causative homozygous 11 bp deletion, c.42_52del, in the TPRN gene in all seven affected individuals. The deletion is located in exon 1 and results in a frameshift and premature protein truncation (p.Gly15AlafsX150). Interestingly, the deleted sequence is part of a repetitive and CG-rich motive predicted to be prone to structural aberrations during crossover formation. We identified another family with progressive ARNSHL linked to this locus, whose affected members were shown to carry a causative 1 bp deletion (c.1347delG) in exon 1 of TPRN. The function of the encoded protein, taperin, is unknown; yet, partial homology to the actin-caping protein phostensin suggests a role in actin dynamics. 相似文献
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Bettina Lorenz-Depiereux Dov Tiosano Gabriele Häusler 《American journal of human genetics》2010,86(2):267-272
The analysis of rare genetic disorders affecting phosphate homeostasis led to the identification of several proteins that are essential for the renal regulation of phosphate homeostasis; for example, fibroblast growth factor 23 (FGF23), which inhibits renal phosphate reabsorption and 1,25-dihydroxyvitamin D synthesis. Here, we report presumable loss-of-function mutations in the ENPP1 gene (ectonucleotide pyrophosphatase/phosphodiesterase) in members of four families affected with hypophosphatemic rickets. We provide evidence for the conclusion that ENPP1 is the fourth gene—in addition to PHEX, FGF23, and DMP1—that, if mutated, causes hypophosphatemic rickets resulting from elevated FGF23 levels. Surprisingly, ENPP1 loss-of-function mutations have previously been described in generalized arterial calcification of infancy, suggesting an as yet elusive mechanism that balances arterial calcification with bone mineralization. 相似文献
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Gabriela Petrof Arti Nanda Jake Howden Takuya Takeichi James R. McMillan Sophia Aristodemou Linda Ozoemena Lu Liu Andrew P. South Celine Pourreyron Dimitra Dafou Laura E. Proudfoot Hejab Al-Ajmi Masashi Akiyama W.H. Irwin McLean Michael A. Simpson Maddy Parsons John A. McGrath 《American journal of human genetics》2014
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Julien Thevenon Mathieu Milh François Feillet Judith St-Onge Yannis Duffourd Clara Jugé Agathe Roubertie Delphine Héron Cyril Mignot Emmanuel Raffo Bertrand Isidor Sandra Wahlen Damien Sanlaville Nathalie Villeneuve Véronique Darmency-Stamboul Annick Toutain Mathilde Lefebvre Mondher Chouchane Frédéric Huet Arnaud Lafon Anne de Saint Martin Gaetan Lesca Salima El Chehadeh Christel Thauvin-Robinet Alice Masurel-Paulet Sylvie Odent Laurent Villard Christophe Philippe Laurence Faivre Jean-Baptiste Rivière 《American journal of human genetics》2014
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Gavin Charlesworth Plamena?R. Angelova Fernando Bartolomé-Robledo Mina Ryten Daniah Trabzuni Maria Stamelou Andrey?Y. Abramov Kailash?P. Bhatia Nicholas?W. Wood 《American journal of human genetics》2015,96(4):657-665
Reports of primary isolated dystonia inherited in an autosomal-recessive (AR) manner, often lumped together as “DYT2 dystonia,” have appeared in the scientific literature for several decades, but no genetic cause has been identified to date. Using a combination of homozygosity mapping and whole-exome sequencing in a consanguineous kindred affected by AR isolated dystonia, we identified homozygous mutations in HPCA, a gene encoding a neuronal calcium sensor protein found almost exclusively in the brain and at particularly high levels in the striatum, as the cause of disease in this family. Subsequently, compound-heterozygous mutations in HPCA were also identified in a second independent kindred affected by AR isolated dystonia. Functional studies suggest that hippocalcin might play a role in regulating voltage-dependent calcium channels. The identification of mutations in HPCA as a cause of AR primary isolated dystonia paves the way for further studies to assess whether “DYT2 dystonia” is a genetically homogeneous condition or not. 相似文献
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Sarah B. Daly Jill E. Urquhart Emma Hilton Edward A. McKenzie Richard A. Kammerer Malcolm Lewis Bronwyn Kerr Helen Stuart Dian Donnai David A. Long Berk Burgu Ozgu Aydogdu Murat Derbent Sixto Garcia-Minaur Willie Reardon Blanca Gener Stavit Shalev Rupert Smith Adrian S. Woolf Graeme C. Black William G. Newman 《American journal of human genetics》2010,87(2):309
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Sarah B. Daly Emma Hilton Richard A. Kammerer Bronwyn Kerr Dian Donnai Berk Burgu Murat Derbent Willie Reardon Stavit Shalev Adrian S. Woolf William G. Newman 《American journal of human genetics》2010,86(6):963-674
Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of anatomical bladder outflow obstruction or overt neurological damage. UFS individuals often have reflux of infected urine from the bladder to the upper renal tract, with a risk of kidney damage and renal failure. Whole-genome SNP mapping in one affected individual defined an autozygous region of 16 Mb on chromosome 10q23-q24, within which a 10 kb deletion encompassing exons 8 and 9 of HPSE2 was identified. Homozygous exonic deletions, nonsense mutations, and frameshift mutations in five further unrelated families confirmed HPSE2 as the causative gene for UFS. Mutations were not identified in four additional UFS patients, indicating genetic heterogeneity. We show that HPSE2 is expressed in the fetal and adult central nervous system, where it might be implicated in controlling facial expression and urinary voiding, and also in bladder smooth muscle, consistent with a role in renal tract morphology and function. Our findings have broader implications for understanding the genetic basis of lower renal tract malformations and voiding dysfunction. 相似文献
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Ziv Gan-Or Naima Bouslam Nazha Birouk Alexandra Lissouba Daniel?B. Chambers Julie Vérièpe Alaura Androschuck Sandra?B. Laurent Daniel Rochefort Dan Spiegelman Alexandre Dionne-Laporte Anna Szuto Meijiang Liao Denise?A. Figlewicz Ahmed Bouhouche Ali Benomar Mohamed Yahyaoui Reda Ouazzani Grace Yoon Nicolas Dupré Oksana Suchowersky Francois?V. Bolduc J.?Alex Parker Patrick?A. Dion Pierre Drapeau Guy?A. Rouleau Bouchra?Ouled?Amar Bencheikh 《American journal of human genetics》2016,98(5):1038-1046
Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous disease characterized by spasticity and weakness of the lower limbs with or without additional neurological symptoms. Although more than 70 genes and genetic loci have been implicated in HSP, many families remain genetically undiagnosed, suggesting that other genetic causes of HSP are still to be identified. HSP can be inherited in an autosomal-dominant, autosomal-recessive, or X-linked manner. In the current study, we performed whole-exome sequencing to analyze a total of nine affected individuals in three families with autosomal-recessive HSP. Rare homozygous and compound-heterozygous nonsense, missense, frameshift, and splice-site mutations in CAPN1 were identified in all affected individuals, and sequencing in additional family members confirmed the segregation of these mutations with the disease (spastic paraplegia 76 [SPG76]). CAPN1 encodes calpain 1, a protease that is widely present in the CNS. Calpain 1 is involved in synaptic plasticity, synaptic restructuring, and axon maturation and maintenance. Three models of calpain 1 deficiency were further studied. In Caenorhabditis elegans, loss of calpain 1 function resulted in neuronal and axonal dysfunction and degeneration. Similarly, loss-of-function of the Drosophila melanogaster ortholog calpain B caused locomotor defects and axonal anomalies. Knockdown of calpain 1a, a CAPN1 ortholog in Danio rerio, resulted in abnormal branchiomotor neuron migration and disorganized acetylated-tubulin axonal networks in the brain. The identification of mutations in CAPN1 in HSP expands our understanding of the disease causes and potential mechanisms. 相似文献