A Segmental Copy Number Loss of the SFMBT1 Gene Is a Genetic Risk for Shunt-Responsive, Idiopathic Normal Pressure Hydrocephalus (iNPH): A Case-Control Study

Sato, Hidenori; Takahashi, Yusuke; Kimihira, Luna; Iseki, Chifumi; Kato, Hiroyuki; Suzuki, Yuya; Igari, Ryosuke; Sato, Hiroyasu; Koyama, Shingo; Arawaka, Shigeki; Kawanami, Toru; Miyajima, Masakazu; Samejima, N; Sato, Shinya; Kameda, Masahiro; Yamada, Shinya; Kita, Daisuke; Kaijima, Mitsunobu; Date, Isao; Sonoda, Yukihiko; Kayama, Takamasa; Kuwana, Nobumasa; Arai, Hajime; Kato, Takeshi

doi:10.1371/journal.pone.0166615

Cited by 34 publications

(24 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An interesting finding in the study was the similar prevalence of the CN loss in intron 2 of the SFMBT1 gene between the fNPH patients and their non-iNPH relatives (9% vs. 9%), despite the allelic variation in SFMBT1 being discovered to be overrepresented in the iNPH patients in a Japanese study cohort [27] and also in Finnish and Norwegian cohorts [28]. This is the first time the SFMBT1 CN loss has been directly compared between the fNPH patients and their relatives.…”

Section: Alcohol Sleep Apnea Sfmbt1 and Apoe ε4mentioning

confidence: 67%

“…In this paper, the probable fNPH patients' ≥ 60-year-old relatives that had no iNPH (fNPH) determined from 44/60 (73%) of the probable and fNPH patients and from 22/49 (45%) of their ≥ 60-year-old non-iNPH relatives by using quantitative PCR and the delta-delta method [27,28].…”

Section: Non-inph Relativesmentioning

confidence: 99%

“…fNPH [ 25 ], but only a few possible risk genes have yet been found. Most promisingly, copy number (CN) loss in intron 2 of the SFMBT1 gene has been reported as being overrepresented among the iNPH patients in Japanese, Finnish and Norwegian study cohorts [ 27 , 28 ]. Also, a loss-of-function mutation in CFAP43 has been found in a Japanese family with multiple iNPH cases [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

Räsänen

Huovinen

Korhonen

et al. 2020

Fluids Barriers CNS

View full text Add to dashboard Cite

Background The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. Methods Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher’s exact test (two-tailed), the Mann–Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. Results Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1–12.9, p = 0.030). Conclusions Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.

show abstract

Section: Alcohol Sleep Apnea Sfmbt1 and Apoe ε4mentioning

confidence: 67%

Section: Non-inph Relativesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

Räsänen

Huovinen

Korhonen

et al. 2020

Fluids Barriers CNS

View full text Add to dashboard Cite

show abstract

“…Targeted genome-wide analyses on the pedigrees of interest offer potential novel discoveries in the future [18]. Until now, the copy number loss of the SFMBT1-gene was the only genetic factor somehow connected to iNPH and may also be worth further study in different populations [19,20].…”

Section: Suboptimal Ependymal Cilia Function With Plausible Environmementioning

confidence: 99%

“…The first genetic finding associated with iNPH-related ventriculomegaly was the copy number loss of SFMBT1, a gene that is expressed e.g. in choroid plexus, which is the primary site of CSF formation [19,20].…”

Section: Introductionmentioning

confidence: 99%

Alzheimer’s Disease-Related Polymorphisms in Shunt-Responsive Idiopathic Normal Pressure Hydrocephalus

Huovinen

Helisalmi

Paananen

et al. 2017

JAD

View full text Add to dashboard Cite

show abstract

Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression

et al. 2022

Advanced Science

View full text Add to dashboard Cite

Genome‐wide association studies have identified 3p21.1 as a robust risk locus for schizophrenia. However, the underlying molecular mechanisms remain elusive. Here a functional regulatory variant (rs2535629) is identified that disrupts CTCF binding at 3p21.1. It is confirmed that rs2535629 is also significantly associated with schizophrenia in Chinese population and the regulatory effect of rs2535629 is validated. Expression quantitative trait loci analysis indicates that rs2535629 is associated with the expression of three distal genes (GLT8D1, SFMBT1, and NEK4) in the human brain, and CRISPR‐Cas9‐mediated genome editing confirmed the regulatory effect of rs2535629 on GLT8D1, SFMBT1, and NEK4. Interestingly, differential expression analysis of GLT8D1, SFMBT1, and NEK4 suggested that rs2535629 may confer schizophrenia risk by regulating SFMBT1 expression. It is further demonstrated that Sfmbt1 regulates neurodevelopment and dendritic spine density, two key pathological characteristics of schizophrenia. Transcriptome analysis also support the potential role of Sfmbt1 in schizophrenia pathogenesis. The study identifies rs2535629 as a plausibly causal regulatory variant at the 3p21.1 risk locus and demonstrates the regulatory mechanism and biological effect of this functional variant, indicating that this functional variant confers schizophrenia risk by altering CTCF binding and regulating expression of SFMBT1, a distal gene which plays important roles in neurodevelopment and synaptic morphogenesis.

show abstract

A Segmental Copy Number Loss of the SFMBT1 Gene Is a Genetic Risk for Shunt-Responsive, Idiopathic Normal Pressure Hydrocephalus (iNPH): A Case-Control Study

Cited by 34 publications

References 27 publications

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

Diabetes is associated with familial idiopathic normal pressure hydrocephalus: a case–control comparison with family members

Alzheimer’s Disease-Related Polymorphisms in Shunt-Responsive Idiopathic Normal Pressure Hydrocephalus

Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression

Contact Info

Product

Resources

About