. 2018 Dec 3;4(6):e291.

doi: 10.1212/NXG.0000000000000291. eCollection 2018 Dec.

Copy number loss in SFMBT1 is common among Finnish and Norwegian patients with iNPH

Ville E Korhonen¹, Seppo Helisalmi¹, Aleksi Jokinen¹, Ilari Jokinen¹, Juha-Matti Lehtola¹, Minna Oinas¹, Kimmo Lönnrot¹, Cecilia Avellan¹, Anna Kotkansalo¹, Janek Frantzen¹, Jaakko Rinne¹, Antti Ronkainen¹, Mikko Kauppinen¹, Antti Junkkari¹, Mikko Hiltunen¹, Hilkka Soininen¹, Mitja Kurki¹, Juha E Jääskeläinen¹, Anne M Koivisto¹, Hidenori Sato¹, Takeo Kato¹, Anne M Remes¹, Per Kristian Eide¹, Ville Leinonen¹

Affiliations

Affiliation

¹ Department of Neurosurgery (V.E.K., A. Jokinen, I.J., J.-M.L., A. Junkkari, J.E.J., V.L.), Kuopio University Hospital and University of Eastern Finland; Institute of Clinical Medicine-Neurology (S.H., M.H., H. Soininen, A.M.K.), University of Eastern Finland, Kuopio; Department of Neurosurgery (M.O., K.L.), University of Helsinki and Helsinki University Hospital; Clinical Neurosciences (C.A., A.K., J.F., J.R.), Department of Neurosurgery, University of Turku and Turku University Hospital; Department of Neurosurgery (A.R.), Tampere University Hospital; Unit of Clinical Neuroscience (M. Kauppinen, V.L.), Neurosurgery, University of Oulu and Medical Research Center, Oulu University Hospital; Institute of Biomedicine (M.H.), University of Eastern Finland, Kuopio; Analytical and Translational Genetics Unit (M. Kurki), Department of Medicine, Massachusetts General Hospital; Program in Medical and Population Genetics (M. Kurki), Broad Institute of MIT and Harvard; Stanley Center for Psychiatric Research (M. Kurki), Broad Institute for Harvard and MIT; Department of Neurology (H. Sato, T.K.), Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine, Japan; Medical Research Center (A.M.R.), Oulu University Hospital, Finland; Unit of Clinical Neuroscience (A.M.R.), Neurology, University of Oulu, Finland; Department of Neurosurgery (P.K.E.), Oslo University Hospital-Rikshospitalet; and Institute of Clinical Medicine (P.K.E.), Faculty of Medicine, University of Oslo, Norway.

PMID: 30584596
PMCID: PMC6283454
DOI: 10.1212/NXG.0000000000000291

Copy number loss in SFMBT1 is common among Finnish and Norwegian patients with iNPH

Ville E Korhonen et al. Neurol Genet. 2018.

. 2018 Dec 3;4(6):e291.

doi: 10.1212/NXG.0000000000000291. eCollection 2018 Dec.

Authors

Affiliation

¹ Department of Neurosurgery (V.E.K., A. Jokinen, I.J., J.-M.L., A. Junkkari, J.E.J., V.L.), Kuopio University Hospital and University of Eastern Finland; Institute of Clinical Medicine-Neurology (S.H., M.H., H. Soininen, A.M.K.), University of Eastern Finland, Kuopio; Department of Neurosurgery (M.O., K.L.), University of Helsinki and Helsinki University Hospital; Clinical Neurosciences (C.A., A.K., J.F., J.R.), Department of Neurosurgery, University of Turku and Turku University Hospital; Department of Neurosurgery (A.R.), Tampere University Hospital; Unit of Clinical Neuroscience (M. Kauppinen, V.L.), Neurosurgery, University of Oulu and Medical Research Center, Oulu University Hospital; Institute of Biomedicine (M.H.), University of Eastern Finland, Kuopio; Analytical and Translational Genetics Unit (M. Kurki), Department of Medicine, Massachusetts General Hospital; Program in Medical and Population Genetics (M. Kurki), Broad Institute of MIT and Harvard; Stanley Center for Psychiatric Research (M. Kurki), Broad Institute for Harvard and MIT; Department of Neurology (H. Sato, T.K.), Hematology, Metabolism, Endocrinology and Diabetology, Yamagata University Faculty of Medicine, Japan; Medical Research Center (A.M.R.), Oulu University Hospital, Finland; Unit of Clinical Neuroscience (A.M.R.), Neurology, University of Oulu, Finland; Department of Neurosurgery (P.K.E.), Oslo University Hospital-Rikshospitalet; and Institute of Clinical Medicine (P.K.E.), Faculty of Medicine, University of Oslo, Norway.

PMID: 30584596
PMCID: PMC6283454
DOI: 10.1212/NXG.0000000000000291

Abstract

Objective: To evaluate the role of the copy number loss in SFMBT1 in a Caucasian population.

Methods: Five hundred sixty-seven Finnish and 377 Norwegian patients with idiopathic normal pressure hydrocephalus (iNPH) were genotyped and compared with 508 Finnish elderly, neurologically healthy controls. The copy number loss in intron 2 of SFMBT1 was determined using quantitative PCR.

Results: The copy number loss in intron 2 of SFMBT1 was detected in 10% of Finnish (odds ratio [OR] = 1.9, p = 0.0078) and in 21% of Norwegian (OR = 4.7, p < 0.0001) patients with iNPH compared with 5.4% in Finnish controls. No copy number gains in SFMBT1 were detected in patients with iNPH or healthy controls. The carrier status did not provide any prognostic value for the effect of shunt surgery in either population. Moreover, no difference was detected in the prevalence of hypertension or T2DM between SFMBT1 copy number loss carriers and noncarriers.

Conclusions: This is the largest and the first multinational study reporting the increased prevalence of the copy number loss in intron 2 of SFMBT1 among patients with iNPH, providing further evidence of its role in iNPH. The pathogenic role still remains unclear, requiring further study.

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Figures

**Figure 1. Flowchart of the study cohort**
Flowchart showing the Finnish and Norwegian cohorts. No difference was detected between the frequency of the genetic variant between shunt-responsive and nonresponsive patients in either Finnish (OR = 1.0, CI 95% 0.44–2.4, p = 0.93) or Norwegian (OR = 0.68, CI 95% 0.31–1.5, p = 0.33) cohort. ^aLost to follow-up (n = 7). ^bLost to follow-up response (n = 63). CI = confidence interval; OR = odds ratio.

**Figure 2. The prevalence of the copy number loss in the SFMBT1 among Finnish and Norwegian patients with iNPH**
The prevalence of the copy number loss in *SFMBT1* among Norwegian iNPH patients is 21% (n = 79/377), 9.9% (n = 56/567) among Finnish iNPH patients, and 5.4% (n = 27/508) among Finnish controls. Statistical significance was observed; Norwegian iNPH patients vs Finnish controls (OR = 4.7, CI 95% 3.0–7.5, p < 0.001), Finnish iNPH patients vs Finnish controls (OR = 1.9, CI 95% 1.2–3.1, p = 0.0078), and Norwegian iNPH patients vs Finnish iNPH patients (OR = 2.5, CI 95% 1.7–3.6, p < 0.001). p < 0.05 was considered statistically significant. The Fisher exact test was used for pairwise comparisons. CI = confidence interval; iNPH = idiopathic normal pressure hydrocephalus; OR = odds ratio.

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Copy number loss in SFMBT1 is common among Finnish and Norwegian patients with iNPH

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Copy number loss in SFMBT1 is common among Finnish and Norwegian patients with iNPH

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