Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification
详细信息 查看全文
- 作者：Sandy Chan Hsu (1)
Renee L. Sears (1)
Roberta R. Lemos (2) (3)
Beatriz Quintáns (2) (4)
Alden Huang (1)
Elizabeth Spiteri (1) (5)
Lisette Nevarez (1)
Catherine Mamah (1) (6)
Mayana Zatz (7)
Kerrie D. Pierce (8)
Janice M. Fullerton (8) (9)
John C. Adair (10)
Jon E. Berner (11)
Matthew Bower (12)
Henry Brodaty (13)
Olga Carmona (14)
Valerija Dobrici? (15)
Brent L. Fogel (1)
Daniel García-Estevez (16)
Jill Goldman (17)
John L. Goudreau (18)
Suellen Hopfer (1) (19)
Milena Jankovi? (15)
Serge Jaumà (20)
Joanna C. Jen (1)
Suppachok Kirdlarp (21)
Joerg Klepper (22)
Vladimir Kosti? (15)
Anthony E. Lang (23)
Agnès Linglart (24)
Melissa K. Maisenbacher (25)
Bala V. Manyam (26)
Pietro Mazzoni (17)
Zofia Miedzybrodzka (27)
Witoon Mitarnun (21)
Philip B. Mitchell (28)
Jennifer Mueller (29)
Ivana Novakovi? (15)
Martin Paucar (30)
Henry Paulson (31)
Sheila A. Simpson (27)
Per Svenningsson (30)
Paul Tuite (32)
Jerrold Vitek (32)
Suppachok Wetchaphanphesat (21)
Charles Williams (25)
Michele Yang (1) (33)
Peter R. Schofield (8) (9)
Jo?o R. M. de Oliveira (34)
María-Jesús Sobrido (2) (4)
Daniel H. Geschwind (1) (35) (36) (38)
Giovanni Coppola (1) (36) (37) - 关键词：Basal ganglia calcification ; Fahr's ; Genetics ; Sequencing ; Mutations
- 刊名：neurogenetics
- 出版年：2013
- 出版时间：February 2013
- 年：2013
- 卷：14
- 期：1
- 页码：11-22
- 参考文献：1. Sobrido MJ, Hopfer S, Geschwind DH (2007) Familial idiopathic basal ganglia calcification. In: Pagon R, Bird T, Dolan C, (eds.) GeneReviews [Internet]. Seattle WA
2. Moskowitz M, Winickoff R, Heinz E (1971) Familial calcification of the basal ganglions: a metabolic and genetic study. N Engl J Med 285(2):72-7 CrossRef
3. Brodaty H, Mitchell P, Luscombe G, Kwok JJ, Badenhop RF, McKenzie R et al (2002) Familial idiopathic basal ganglia calcification (Fahr's disease) without neurological, cognitive and psychiatric symptoms is not linked to the IBGC1 locus on chromosome 14q. Hum Genet 110(1):8-4 CrossRef
4. Koller WC, Cochran JW, Klawans HL (1979) Calcification of the basal ganglia: computerized tomography and clinical correlation. Neurology 29(3):328-33
5. Harrington MG, Macpherson P, McIntosh WB, Allam BF, Bone I (1981) The significance of the incidental finding of basal ganglia calcification on computed tomography. J Neurol Neurosurg Psychiatry 44(12):1168-170
6. F?rstl H, Krumm B, Eden S, Kohlmeyer K (1991) What is the psychiatric significance of bilateral basal ganglia mineralization? Biol Psychiatry 29(8):827-33
7. Geschwind D, Loginov M, Stern J (1999) Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease). Am J Hum Genet 65(3):764-72 CrossRef
8. Volpato CBB, De Grandi A, Buffone E, Facheris M, Gebert U, Schifferle G et al (2009) 2q37 as a susceptibility locus for idiopathic basal ganglia calcification (IBGC) in a large South Tyrolean family. J Mol Neurosci 39(3):346-53
9. Dai X, Gao Y, Xu Z, Cui X, Liu J, Li Y et al (2010) Identification of a novel genetic locus on chromosome 8p21.1–q11.23 for idiopathic basal ganglia calcification. Am J Med Genet B Neuropsychiatr Genet 153B(7):1305-310 CrossRef
10. Wang C, Li Y, Shi L, Ren J, Patti M, Wang T et al (2012) Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis. Nature Genetics 44:254-56
11. Ng PC, Henikoff S (2003) SIFT: predicting amino acid changes that affect protein function. Nucl Acids Res 31(13):3812-814
12. Desmet FO, Hamroun D, Lalande M, Collod-Béroud G, Claustres M, Béroud C (2009) Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucl Acids Res 37(9):e67
13. Adzhubei IA, Schmidt S, Peshkin L, Ramensky VE, Gerasimova A, Bork P et al (2010) A method and server for predicting damaging missense mutations. Nat Methods 7(4):248-49
14. B?ttger P, Pedersen L (2011) Mapping of the minimal inorganic phosphate transporting unit of human PiT2 suggests a structure universal to PiT-related proteins from all kingdoms of life. BMC Biochem 12(1):21
15. Oliveira JR, Spiteri E, Sobrido MJ, Hopfer S, Klepper J, Voit T et al (2004) Genetic heterogeneity in familial idiopathic basal ganglia calcification (Fahr disease). Neurology 63(11):2165-167
16. Kosti? VS, Luki?-Je?menica M, Novakovi? I, Dobri?i? V, Brajkovi? L, Krajinovi? M et al (2011) Exclusion of linkage to chromosomes 14q, 2q37 and 8p21.1–q11.23 in a Serbian family with idiopathic basal ganglia calcification. J Neurol 258(9):1637-642 - 作者单位：Sandy Chan Hsu (1)
Renee L. Sears (1)
Roberta R. Lemos (2) (3)
Beatriz Quintáns (2) (4)
Alden Huang (1)
Elizabeth Spiteri (1) (5)
Lisette Nevarez (1)
Catherine Mamah (1) (6)
Mayana Zatz (7)
Kerrie D. Pierce (8)
Janice M. Fullerton (8) (9)
John C. Adair (10)
Jon E. Berner (11)
Matthew Bower (12)
Henry Brodaty (13)
Olga Carmona (14)
Valerija Dobrici? (15)
Brent L. Fogel (1)
Daniel García-Estevez (16)
Jill Goldman (17)
John L. Goudreau (18)
Suellen Hopfer (1) (19)
Milena Jankovi? (15)
Serge Jaumà (20)
Joanna C. Jen (1)
Suppachok Kirdlarp (21)
Joerg Klepper (22)
Vladimir Kosti? (15)
Anthony E. Lang (23)
Agnès Linglart (24)
Melissa K. Maisenbacher (25)
Bala V. Manyam (26)
Pietro Mazzoni (17)
Zofia Miedzybrodzka (27)
Witoon Mitarnun (21)
Philip B. Mitchell (28)
Jennifer Mueller (29)
Ivana Novakovi? (15)
Martin Paucar (30)
Henry Paulson (31)
Sheila A. Simpson (27)
Per Svenningsson (30)
Paul Tuite (32)
Jerrold Vitek (32)
Suppachok Wetchaphanphesat (21)
Charles Williams (25)
Michele Yang (1) (33)
Peter R. Schofield (8) (9)
Jo?o R. M. de Oliveira (34)
María-Jesús Sobrido (2) (4)
Daniel H. Geschwind (1) (35) (36) (38)
Giovanni Coppola (1) (36) (37)
1. Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
2. Fundación Pública Galega de Medicina Xenómica and Clinical University Hospital of Santiago de Compostela-SERGAS, Santiago de Compostela, Spain
3. Keizo Asami Laboratory and Biological Sciences Graduate Program, Federal University of Pernambuco, Recife, Brazil
4. Center for Biomedical Research on Rare Diseases (CIBERER) Institute of Health Carlos III, Valencia, Spain
5. Department of Pathology and Laboratory Science, Cedars Sinai Medical Center, Los Angeles, CA, USA
6. Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
7. Human Genome Center, University of S?o Paulo, S?o Paulo, Brazil
8. Neuroscience Research Australia, Sydney, Australia
9. School of Medical Sciences, The University of New South Wales, Sydney, Australia
10. Department of Neurology, University of New Mexico, Albuquerque, NM, USA
11. Woodinville Psychiatric Association, Woodinville, WA, USA
12. Division of Genetics and Metabolism, University of Minnesota Medical Center, Fairview, Minneapolis, MN, USA
13. Centre for Healthy Brain Ageing, School of Psychiatry, The University of New South Wales, Sydney, Australia
14. Department of Neurology, Hospital of Figueres, Girona, Spain
15. Neurology Clinic, University Clinical Center, Belgrade, Serbia
16. Department of Neurology, Monforte de Lemos Hospital-SERGAS, Lugo, Spain
17. The Center for Parkinson’s Disease & Related Disorders, Columbia University Medical Center, New York, NY, USA
18. Department of Neurology, Michigan State University, East Lansing, MI, USA
19. Pennsylvania State University, University Park, PA, USA
20. Department of Neurology, Hospital of Bellvitge, Barcelona, Spain
21. Division of Medicine, Buriram Hospital, Buriram, Thailand
22. Klinikum Aschaffenburg, Aschaffenburg, Germany
23. The Movement Disorders Center and the Edomond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, Toronto, Canada
24. APHP, Center for Rare Disorders of the Calcium and Phosphorus Metabolism, Bicêtre-Paris-Sud Hospital; INSERM U986, Paris, France
25. Department of Pediatrics, University of Florida, Gainesville, FL, USA
26. Department of Neurology, Penn State Milton S. Hershey College of Medicine, Odessa, FL, USA
27. Medical Genetics Group, School of Medicine & Dentistry, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, UK, AB25 2ZD
28. School of Psychiatry, The University of New South Wales and Black Dog Institute, Sydney, Australia
29. Division of Genetics and Metabolism, University of Florida, Gainesville, FL, USA
30. Translational Neuropharmacology, Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute and Neurology Clinic, Karolinska Hospital, Huddinge, Stockholm, Sweden
31. Department of Neurology, University of Michigan, Ann Arbor, MI, USA
32. Department of Neurology, University of Minnesota Medical Center, Fairview, MN, USA
33. Department of Pediatrics, Children’s Hospital Colorado and the University of Colorado Denver, Aurora, CO, USA
34. Neuropsychiatry Department and Keizo Asami Laboratory, Federal University of Pernambuco, Recife, Brazil
35. Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
36. Department of Psychiatry and Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, USA
38. Program in Neurogenetics, Department of Neurology, 2306 Gonda, 695 Charles Young Drive South, Los Angeles, CA, 90095, USA
37. Semel Institute for Neuroscience and Human Behavior, 1524 Gonda, 695 Charles Young Drive South, Los Angeles, CA, 90095, USA - ISSN：1364-6753
文摘
Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41?% of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation.