. 2025 Sep 3;148(9):3252-3265.

doi: 10.1093/brain/awaf134.

Intronic FGF14 GAA repeat expansions impact progression and survival in multiple system atrophy

Viorica Chelban^{1

2}, David Pellerin^{1

3

4}, Nirosen Vijiaratnam^{5

6}, Hamin Lee¹, Yen Yee Goh¹, Lauren Brown¹, Sara Sambin^{7

8}, Danielle Seilhean⁹, Stephane Lehericy^{7

10}, Pablo Iruzubieta^{1

4

11

12}, Rahema Mohammad¹, Eleanor Self¹, Annarita Scardamaglia¹, Cameron Lee¹, Miriama Ostrozovicova¹, Marie-Josée Dicaire⁴, Christine Girges¹³, Emil K Gustavsson^{14

15}, David Murphy¹³, Toby Curless^{13

16}, Joshua Laß¹⁷, Joanne Trinh¹⁷, Timothy Rittman^{18

19}, James B Rowe^{18

19

20}, Marios Hadjivassiliou²¹, Neil Archibald²², Matt C Danzi³, Catherine Ashton^{4

23}, Virginie Roth²⁴, Marion Wandzel²⁴, Warren A Cheung²⁵, Djordje O Gveric²⁶, Bart De Vil^{27

28

29}, Jordan Follett³⁰, P Nigel Leigh³¹, Lukas Beichert^{32

33}, Tomi Pastinen³⁴, Céline Bonnet^{24

35}, Mathilde Renaud^{34

35

36}, Wassilios G Meissner^{37

38

39

40}, Anne Sieben^{27

28

41}, David Crosiers^{28

29}, Patrick Cras^{28

29}, Stephan Zuchner³, Jean-Christophe Corvol^{7

8}, Matthew J Farrer³⁰, Matthis Synofzik^{32

33}, Bernard Brais^{4

42}, Tom Warner^{13

16}, Huw R Morris¹³, Zane Jaunmuktane^{13

16

43}, Tom Foltynie¹³, Henry Houlden¹

Affiliations

¹ Neuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
² Neurobiology and Medical Genetics Laboratory, 'Nicolae Testemitanu' State University of Medicine and Pharmacy, Chisinau MD-2004, Republic of Moldova.
³ Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
⁴ Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, QC H3A 2B4, Canada.
⁵ Clinical Research Centre for Movement Disorders and Gait, Kingston Centre, Parkinson's Foundation Centre of Excellence, Monash Health, Cheltenham, VIC 3192, Australia.
⁶ Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC 3168, Australia.
⁷ Institut du Cerveau-Paris BrainInstitute-ICM, Inserm, CNRS, Sorbonne Université, Paris 75651, France.
⁸ Department of Neurology, Assistance Publique Hôpitaux de Paris, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Paris 75651, France.
⁹ Département de Neuropathologie, Institut de Neurologie, DMU Neurosciences, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, Paris 75651, France.
¹⁰ Department of Neuroradiology, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris 75013, France.
¹¹ Department of Neurology, Donostia University Hospital, Biogipuzkoa Health Research Institute, Donostia-San Sebastián 20014, Spain.
¹² CIBERNED Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Instituto de Salud Carlos III (CIBER-CIBERNED-ISCIII), Madrid 28029, Spain.
¹³ Department Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
¹⁴ Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London WC1N 3BG, UK.
¹⁵ UK Dementia Research Institute, The University of Cambridge, Cambridge CB2 0AH, UK.
¹⁶ Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK.
¹⁷ Institute of Neurogenetics, University of Lübeck, Lübeck 23538, Germany.
¹⁸ Department of Clinical Neurosciences, Cambridge University, Cambridge CB2 0SZ, UK.
¹⁹ Department of Neurology, Cambridge University Hospitals NHS Trust, Cambridge CB2 0QQ, UK.
²⁰ MRC Cognition and Brain Sciences Unit, Cambridge University, Cambridge CB2 7EF, UK.
²¹ Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust, Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
²² Department of Neurology, South Tees NHS Foundation Trust, Middlesbrough TS4 3BW, UK.
²³ Department of Neurology, Royal Perth Hospital, Perth, WA 6000, Australia.
²⁴ Laboratoire de Génétique, CHRU de Nancy, Nancy 54511, France.
²⁵ Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO 64108, USA.
²⁶ Department of Brain Sciences, Imperial College London, London W12 0NN, UK.
²⁷ Neuropathology Lab, IBB-NeuroBiobank BB190113, Born Bunge Institute, Antwerp 2610, Belgium.
²⁸ Faculty of Medicine and Health Sciences, Translational Neurosciences, Born-Bunge Institute, University of Antwerp, Antwerp 2610, Belgium.
²⁹ Department of Neurology, Antwerp University Hospital, Edegem 2650, Belgium.
³⁰ Department of Neurology, McKnight Brain Institute, University of Florida, Florida, FL 32610, USA.
³¹ Department of Neuroscience, Brighton and Sussex Medical School, Brighton BN1 9PX, UK.
³² German Center for Neurodegenerative Diseases (DZNE), Tübingen 72076, Germany.
³³ Division of Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen 72076, Germany.
³⁴ Service de Génétique Clinique, CHRU de Nancy, Nancy 54511, France.
³⁵ INSERM-U1256 NGERE, Université de Lorraine, Nancy 54500, France.
³⁶ Service de Neurologie, CHRU de Nancy, Nancy 54511, France.
³⁷ Service de Neurologie-Maladies Neurodégénératives, IMNc, CRMR AMS, CHU de Bordeaux, Bordeaux 33076, France.
³⁸ CNRS, IMN, UMR 5293, University of Bordeaux, Bordeaux F-33000, France.
³⁹ Department of Medicine, University of Otago, Christchurch 9016, New Zealand.
⁴⁰ New Zealand Brain Research Institute, Christchurch 8011, New Zealand.
⁴¹ Department of Pathology, Antwerp University Hospital-UZA, Antwerp 2650, Belgium.
⁴² Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada.
⁴³ Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London WC1N 3BG, UK.

PMID: 40239008
PMCID: PMC12404725
DOI: 10.1093/brain/awaf134

Intronic FGF14 GAA repeat expansions impact progression and survival in multiple system atrophy

Viorica Chelban et al. Brain. 2025.

. 2025 Sep 3;148(9):3252-3265.

doi: 10.1093/brain/awaf134.

Authors

Affiliations

¹ Neuromuscular Disease Department, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
² Neurobiology and Medical Genetics Laboratory, 'Nicolae Testemitanu' State University of Medicine and Pharmacy, Chisinau MD-2004, Republic of Moldova.
³ Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
⁴ Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, QC H3A 2B4, Canada.
⁵ Clinical Research Centre for Movement Disorders and Gait, Kingston Centre, Parkinson's Foundation Centre of Excellence, Monash Health, Cheltenham, VIC 3192, Australia.
⁶ Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC 3168, Australia.
⁷ Institut du Cerveau-Paris BrainInstitute-ICM, Inserm, CNRS, Sorbonne Université, Paris 75651, France.
⁸ Department of Neurology, Assistance Publique Hôpitaux de Paris, CIC Neurosciences, Hôpital Pitié-Salpêtrière, Paris 75651, France.
⁹ Département de Neuropathologie, Institut de Neurologie, DMU Neurosciences, Groupe Hospitalier Pitié-Salpêtrière, 47-83 boulevard de l'Hôpital, Paris 75651, France.
¹⁰ Department of Neuroradiology, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris 75013, France.
¹¹ Department of Neurology, Donostia University Hospital, Biogipuzkoa Health Research Institute, Donostia-San Sebastián 20014, Spain.
¹² CIBERNED Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas, Instituto de Salud Carlos III (CIBER-CIBERNED-ISCIII), Madrid 28029, Spain.
¹³ Department Clinical and Movement Neuroscience, UCL Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK.
¹⁴ Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London WC1N 3BG, UK.
¹⁵ UK Dementia Research Institute, The University of Cambridge, Cambridge CB2 0AH, UK.
¹⁶ Queen Square Brain Bank for Neurological Disorders, UCL Queen Square Institute of Neurology, London WC1N 1PJ, UK.
¹⁷ Institute of Neurogenetics, University of Lübeck, Lübeck 23538, Germany.
¹⁸ Department of Clinical Neurosciences, Cambridge University, Cambridge CB2 0SZ, UK.
¹⁹ Department of Neurology, Cambridge University Hospitals NHS Trust, Cambridge CB2 0QQ, UK.
²⁰ MRC Cognition and Brain Sciences Unit, Cambridge University, Cambridge CB2 7EF, UK.
²¹ Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust, Royal Hallamshire Hospital, Sheffield S10 2JF, UK.
²² Department of Neurology, South Tees NHS Foundation Trust, Middlesbrough TS4 3BW, UK.
²³ Department of Neurology, Royal Perth Hospital, Perth, WA 6000, Australia.
²⁴ Laboratoire de Génétique, CHRU de Nancy, Nancy 54511, France.
²⁵ Genomic Medicine Center, Children's Mercy Kansas City, Kansas City, MO 64108, USA.
²⁶ Department of Brain Sciences, Imperial College London, London W12 0NN, UK.
²⁷ Neuropathology Lab, IBB-NeuroBiobank BB190113, Born Bunge Institute, Antwerp 2610, Belgium.
²⁸ Faculty of Medicine and Health Sciences, Translational Neurosciences, Born-Bunge Institute, University of Antwerp, Antwerp 2610, Belgium.
²⁹ Department of Neurology, Antwerp University Hospital, Edegem 2650, Belgium.
³⁰ Department of Neurology, McKnight Brain Institute, University of Florida, Florida, FL 32610, USA.
³¹ Department of Neuroscience, Brighton and Sussex Medical School, Brighton BN1 9PX, UK.
³² German Center for Neurodegenerative Diseases (DZNE), Tübingen 72076, Germany.
³³ Division of Translational Genomics of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Tübingen 72076, Germany.
³⁴ Service de Génétique Clinique, CHRU de Nancy, Nancy 54511, France.
³⁵ INSERM-U1256 NGERE, Université de Lorraine, Nancy 54500, France.
³⁶ Service de Neurologie, CHRU de Nancy, Nancy 54511, France.
³⁷ Service de Neurologie-Maladies Neurodégénératives, IMNc, CRMR AMS, CHU de Bordeaux, Bordeaux 33076, France.
³⁸ CNRS, IMN, UMR 5293, University of Bordeaux, Bordeaux F-33000, France.
³⁹ Department of Medicine, University of Otago, Christchurch 9016, New Zealand.
⁴⁰ New Zealand Brain Research Institute, Christchurch 8011, New Zealand.
⁴¹ Department of Pathology, Antwerp University Hospital-UZA, Antwerp 2650, Belgium.
⁴² Department of Human Genetics, McGill University, Montreal, QC H3A 0G4, Canada.
⁴³ Division of Neuropathology, National Hospital for Neurology and Neurosurgery, University College London NHS Foundation Trust, London WC1N 3BG, UK.

PMID: 40239008
PMCID: PMC12404725
DOI: 10.1093/brain/awaf134

Abstract

Partial phenotypic overlap has been suggested between multiple system atrophy and spinocerebellar ataxia 27B, the autosomal dominant ataxia caused by an intronic GAA•TTC repeat expansion in FGF14. In this study, we investigated the frequency of FGF14 GAA•TTC repeat expansion in clinically diagnosed and pathologically confirmed multiple system atrophy cases. We screened 657 multiple system atrophy cases (193 clinically diagnosed and 464 pathologically confirmed) and 1003 controls. The FGF14 repeat locus was genotyped using long-range PCR and bidirectional repeat-primed PCRs, and expansions were confirmed with targeted long-read Oxford Nanopore Technologies sequencing. We identified 19 multiple system atrophy cases carrying an FGF14 GAA≥250 expansion (2.89%, n = 19/657), a significantly higher frequency than in controls (1.40%, n = 12/1003) (P = 0.04). Long-read Oxford Nanopore Technologies sequencing confirmed repeat sizes and polymorphisms detected by PCR, with high concordance (Pearson's r = 0.99, P < 0.0001). Seven multiple system atrophy patients had a pathogenic FGF14 GAA≥300 expansion (five pathologically confirmed and two clinically diagnosed), and 12 had intermediate GAA250-299 expansion (six pathologically confirmed and six clinically diagnosed). A similar proportion of cerebellar-predominant and parkinsonism-predominant multiple system atrophy cases had FGF14 expansions. Multiple system atrophy patients carrying an FGF14 GAA≥250 expansion exhibited severe gait ataxia, autonomic dysfunction and parkinsonism, in keeping with a multiple system atrophy phenotype, with a faster progression to falls (P = 0.03) and regular wheelchair use (P = 0.02) in comparison to the multiple system atrophy cases without FGF14 GAA expansion. The length of the GAA•TTC repeat expansion lengths was inversely correlated with survival in multiple system atrophy patients (r = -0.67; P = 0.02) but not with age of onset. Therefore, screening for FGF14 GAA•TTC repeat expansion should be considered for multiple system atrophy patients with rapid loss of mobility and for complete diagnostic accuracy at inclusion in disease-modifying multiple system atrophy drug trials.

Keywords: FGF14 GAA ataxia; multiple system atrophy; spinocerebellar ataxia 27B.

PubMed Disclaimer

Conflict of interest statement

J.B.R. has undertaken remunerated consultancy or advisory board roles for Astronautx, Astex, Asceneuron, Alector, CumulusNeuro, Curasen, Eisai, Prevail and SV Health and has received academic grant income from AstraZeneca, Lilly, GSJ and Janssen as partners in Dementias Platform UK. M.S. has received consultancy honoraria from Ionis, UCB, Prevail, Orphazyme, Biogen, Servier, Reata, GenOrph, AviadoBio, Biohaven, Zevra, Lilly and Solaxa, all unrelated to the present manuscript. W.G.M. has received consultancy fees from Lundbeck, Takeda, Inhibikase, GE and Koneksa. H.R.M. is employed by UCL; in the last 12 months he reports paid consultancy from Roche, Aprinoia, AI Therapeutics and Amylyx; lecture fees/honoraria from BMJ, Kyowa Kirin and the Movement Disorders Society; and research grants from Parkinson's UK, Cure Parkinson's Trust, PSP Association, Medical Research Council and Michael J. Fox Foundation. Dr Morris is a co-applicant on a patent application related to C9ORF72-Method for diagnosing a neurodegenerative disease (PCT/GB2012/052140). T.F. has served on Advisory Boards for Peptron, Voyager Therapeutics, Handl therapeutics, Gain therapeutics, Living Cell Technologies, Abbvie, Bluerock, Bayer and Bial. He has received honoraria for talks sponsored by Bayer, Bial, Profile Pharma, Boston Scientific and Novo Nordisk. All other authors report no competing interests.

Figures

**Figure 1**
**Study flowchart diagram.** MSA = multiple system atrophy; ONT = Oxford Nanopore Technologies; RP-PCR = repeat-primed PCR.

**Figure 2**
**Flowchart diagram of genetic tests performed in this study for confirmation and validation of *FGF14* GAA•TTC repeat expansions.** MSA-C = multiple system atrophy cerebellar subtype; MSA-P = multiple system atrophy parkinsonian subtype; OPCA = olivopontocerebellar atrophy; SND = striatonigral degeneration.

**Figure 3**
*FGF14* allelic distribution in MSA patients and correlation with survival. (A) *FGF14* allelic distribution in all MSA patients included in this study. Allele distribution of the *FGF14* repeat locus in 657 MSA cases (1314 chromosomes). Among the patients with GAA-*FGF14*-positive MSA, seven were heterozygous for a GAA_≥300 expansions, and 12 were heterozygous for a GAA_250–299 expansion. The density plot shows allele-size frequencies, with higher densities indicating greater frequencies. The box-and-whisker plot shows the allelic distribution in patients. The box indicates the 25th percentile (first quartile), the median and the 75th percentile (third quartile), and the whiskers indicate the 2.5th and 97.5th percentiles. Outliers are represented by black dots. Expanded alleles consisting of non-GAA-pure repeats are represented by red triangles, and the red line marks the threshold of GAA₃₀₀ repeat units. (B) Nanopore repeat size estimates concur with PCR estimates. Comparison of repeat size estimates by LR-PCR and ONT adaptive sequencing targeting for 14 individuals carrying a repeat expansion. (C) Correlation of repeat size in DNA from brain and blood matched samples. Correlation between size of the *FGF14* GAA•TTC repeat measured in matched samples from individuals with blood-extracted DNA and brain-extracted DNA (Pearson's r = 0.9, P < 0.0001). (D) Correlation between allele size and survival. Statistically significant negative correlation between size of the *FGF14* GAA•TTC repeat expansion and survival (calculated from disease onset until death) in patients with MSA (Pearson's r = −0.67; P = 0.02). LR-PCR = long-range PCR; ONT = Oxford Nanopore Technologies; MSA = multiple system atrophy.

**Figure 4**
**MRI features in *FGF14* GAA_≥300 patients with MSA.** *Top panels* show MRI features in case C1 at age 59, 1 year from onset of symptoms, and *bottom panels* show MRI features in P3 at age 55, 5 years from onset of symptoms. (A and C) Axial T2-weighted images. (B and F) Sagittal T1-weighted images. (E and G) axial proton-density images. (D and H) Axial susceptibility-weighted images. Case C1 had a clinically established diagnosis of multiple system atrophy parkinsonian subtype and *FGF14* GAA₃₅₃ repeat expansion. Case P3 had a neuropathologically established diagnosis of mixed type of multiple system atrophy and *FGF14* GAA₃₂₆ repeat expansion. ‘Hot-cross-bun’ signs (A and E) and cerebellar atrophy (B and F) are present in both cases, more pronounced in Case P3. Hypointensity of the putamen in Case C1 is seen in is seen in C and D.

**Figure 5**
**Pathological findings in MSA cases with *FGF14* GAA repeat expansions.** Findings in *FGF14* GAA_≥300 and *FGF14* GAA_250–299 patients with MSA. (A–E) Case P7 (281 GAA repeats). (A) Severe putaminal atrophy, typical of MSA, is seen on the coronal section (red arrow). (B) Substantia nigra in the midbrain shows prominent pallor (red arrow). (C) The height of the pontine base is preserved (blue arrow). (D) The inferior olivary nucleus is clearly visible (blue arrow). (E) In the cerebellum at the level of the dentate nucleus, there is no evidence of significant white matter atrophy (blue arrow), the cerebellar cortex shows no apparent atrophy (blue asterisk), and the dentate nucleus is unremarkable. The macroscopic appearances are typical of MSA-SND. (F–R) Case P10 (277 GAA repeats). (F) Hippocampus shows no atrophy. (G) In the tail of the caudate nucleus (blue rectangle in F), there are glial cytoplasmic inclusions in the grey matter and within striato-pallidal fibres (red arrow), in addition to neuronal cytoplasmic inclusions in the grey matter (magenta arrow). (H) In the white matter of the parahippocampal gyrus (red rectangle in F) and adjacent gyri, there are occasional glial cytoplasmic inclusions. (I) In the substantia nigra, there is prominent depletion of pigmented neurons, with neuromelanin deposition freely in the neuropil (black arrow); occasional residual pigmented neurons contain diffuse cytoplasmic α-synuclein aggregates, and there are occasional glial cytoplasmic inclusions across the midbrain (red arrow). (J) In the pontine base, there is a prominent atrophy of the transverse fibres and pontine base nuclei (red rectangle in J). (K) There are numerous neuronal cytoplasmic and intranuclear inclusions (magenta arrow) in the pontine nuclei, and glial cytoplasmic inclusions (red arrow) in the nuclei and transverse fibres. (L–N) In the medulla, there are frequent diffuse neuronal cytoplasmic inclusions in the inferior olivary nucleus (blue rectangle in L and magenta arrow in M) and glial cytoplasmic inclusions in the white matter (red rectangle in L and red arrow in N). In the cerebellum (O, P and R), there is a moderate depletion of Purkinje cells, but good preservation of the granule cells, with occasional glial cytoplasmic inclusions (red arrow in P) in the cortex (magenta rectangle in O), and numerous glial cytoplasmic inclusions (red arrow in R) in the cerebellar white matter (magenta rectangle in O). The histological appearances are typical of MSA with equal SND and OPCA involvement. (S and T) α-Synuclein immunohistochemistry in findings in *FGF14* GAA_≥300-positive patients with MSA show numerous intra-oligodendroglial inclusions in the cerebellum (S) and medulla oblongata (T). Scale bars: 3 mm in F and O; 50 µm in G–I, K, M, N, P and R; 400 µm in J; 0.7 mm in L; 40 µm in S and T. MSA = multiple system atrophy; MSA-C = multiple system atrophy cerebellar subtype; MSA-P = multiple system atrophy parkinsonian subtype; OPCA = olivopontocerebellar atrophy; SND = striatonigral degeneration.

See this image and copyright information in PMC

References

1. Goh YY, Saunders E, Pavey S, et al. Multiple system atrophy. Pract Neurol. 2023;23:208–221. - PMC - PubMed
1. Papp MI, Kahn JE, Lantos PL. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci. 1989;94:79–100. - PubMed
1. Spillantini MG, Anthony Crowther R, Jakes R, et al. Filamentous α-synuclein inclusions link multiple system atrophy with Parkinson’s disease and dementia with Lewy bodies. Neurosci Lett. 1998;251:205–208. - PubMed
1. Gilman S, Wenning GK, Low PA, et al. Second consensus statement on the diagnosis of multiple system atrophy. Neurology. 2008;71:670–676. - PMC - PubMed
1. Koga S, Aoki N, Uitti RJ, et al. When DLB, PD, and PSP masquerade as MSA: An autopsy study of 134 patients. Neurology. 2015;85:404–412. - PMC - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Intronic FGF14 GAA repeat expansions impact progression and survival in multiple system atrophy

Affiliations

Intronic FGF14 GAA repeat expansions impact progression and survival in multiple system atrophy

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous

Abstract

Conflict of interest statement

Figures

Similar articles

References

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous