uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Wesström, Jan
Publications (7 of 7) Show all publications
Bondeson, M.-L., Ericson, K., Gudmundsson, S., Ameur, A., Ponten, F., Wesström, J., . . . Wilbe, M. (2017). A nonsense mutation in CEP55 defines a new locus for a Meckel-like syndrome, an autosomal recessive lethal fetal ciliopathy.. Clinical Genetics, 92(5), 510-516
Open this publication in new window or tab >>A nonsense mutation in CEP55 defines a new locus for a Meckel-like syndrome, an autosomal recessive lethal fetal ciliopathy.
Show others...
2017 (English)In: Clinical Genetics, ISSN 0009-9163, E-ISSN 1399-0004, Vol. 92, no 5, p. 510-516Article in journal (Refereed) Published
Abstract [en]

Mutations in genes involved in the cilium-centrosome complex are called ciliopathies. Meckel-Gruber syndrome (MKS) is a ciliopathic lethal autosomal recessive syndrome characterized by genetically and clinically heterogeneous manifestations, including renal cystic dysplasia, occipital encephalocele and polydactyly. Several genes have previously been associated with MKS and MKS-like phenotypes, but there are still genes remaining to be discovered. We have used whole exome sequencing (WES) to uncover the genetics of a suspected autosomal recessive Meckel syndrome phenotype in a family with two affected fetuses. RNA studies and histopathological analysis was performed for further delineation. WES lead to identification of a homozygous nonsense mutation c.256C>T (p.Arg86*) in CEP55 (centrosomal protein of 55 kDa) in the affected fetus. The variant has previously been identified in carriers in low frequencies, and segregated in the family. CEP55 is an important centrosomal protein required for the mid-body formation at cytokinesis. Our results expand the list of centrosomal proteins implicated in human ciliopathies and provide evidence for an essential role of CEP55 during embryogenesis and development of disease.

Keywords
CEP55, Meckel-like, ciliopathy, cytokinesis, whole exome sequencing
National Category
Clinical Medicine Clinical Laboratory Medicine
Research subject
Pathology
Identifiers
urn:nbn:se:uu:diva-318127 (URN)10.1111/cge.13012 (DOI)000412590300007 ()28295209 (PubMedID)
Funder
Magnus Bergvall FoundationLars Hierta Memorial FoundationSwedish Society for Medical Research (SSMF)
Available from: 2017-03-23 Created: 2017-03-23 Last updated: 2019-01-04Bibliographically approved
Kullinger, M., Wesström, J., Kieler, H. & Skalkidou, A. (2017). Maternal and fetal characteristics affect discrepancies between pregnancy-dating methods: a population-based cross-sectional register study. Acta Obstetricia et Gynecologica Scandinavica, 96(1), 86-95
Open this publication in new window or tab >>Maternal and fetal characteristics affect discrepancies between pregnancy-dating methods: a population-based cross-sectional register study
2017 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 96, no 1, p. 86-95Article in journal (Refereed) Published
Abstract [en]

IntroductionGestational age is estimated by ultrasound using fetal size as a proxy for age, although variance in early growth affects reliability. The aim of this study was to identify characteristics associated with discrepancies between last menstrual period-based (EDD-LMP) and ultrasound-based (EDD-US) estimated delivery dates. Material and methodsWe identified all singleton births (n=1201679) recorded in the Swedish Medical Birth Register in 1995-2010, to assess the association between maternal/fetal characteristics and large negative and large positive discrepancies (EDD-LMP earlier than EDD-US and 10th percentile in the discrepancy distribution vs. EDD-LMP later than EDD-US and 90th percentile). Analyses were adjusted for age, parity, height, body mass index, smoking, and employment status. ResultsWomen with a body mass index >40kg/m(2) had the highest odds for large negative discrepancies (-9 to -20days) [odds ratio (OR) 2.16, 95% CI 2.01-2.33]. Other factors associated with large negative discrepancies were: diabetes, young maternal age, multiparity, body mass index between 30 and 39.9kg/m(2) or <18.5kg/m(2), a history of gestational diabetes, female fetus, shorter stature (<-1SD), a history of preeclampsia, smoking or snuff use, and unemployment. Large positive discrepancies (+4 to +20days) were associated with male fetus (OR 1.80, 95% CI 1.77-1.83), age 30years, multiparity, not living with a partner, taller stature (>+1 SD), and unemployment. ConclusionsSeveral maternal and fetal characteristics were associated with discrepancies between dating methods. Systematic associations of discrepancies with maternal height, fetal sex, and partly obesity, may reflect an influence on the precision of the ultrasound estimate due to variance in early growth.

Keywords
Pregnancy dating, pregnancy, gestational age, ultrasonography, prenatal, menstruation, female, humans
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-315826 (URN)10.1111/aogs.13034 (DOI)000391980100011 ()27696340 (PubMedID)
Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2018-03-15Bibliographically approved
Wesström, J., Ulfberg, J., Sundström Poromaa, I. & Lindberg, E. (2014). Periodic Limb Movements are Associated with Vasomotor Symptoms. Journal of Clinical Sleep Medicine (JCSM), 10(1), 15-20
Open this publication in new window or tab >>Periodic Limb Movements are Associated with Vasomotor Symptoms
2014 (English)In: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, Vol. 10, no 1, p. 15-20Article in journal (Refereed) Published
Abstract [en]

Study objectives:

Periodic limb movements (PLMs) are characterized by involuntary movements of the lower extremity during sleep. The etiology of PLM has been suggested to involve the dopaminergic system which, in turn, can be modulated by estrogen. It is currently unknown whether PLMs are associated with the menopausal transition and/or concomitant vasomotor symptoms. The aim of the present study was to examine if objectively-diagnosed PLMs (with and without arousals) are more common in postmenopausal women or in women with vasomotor symptoms. Another aim was to analyze the influence of PLMs on self-reported HRQoL.

Methods:

A community-based sample of 348 women underwent full-night polysomnography. PLMs (index > 15) and associated arousals (PLM arousal index > 5) were evaluated according to AASM scoring rules. Health related quality of life was measured using the SF-36 questionnaire. The occurrence of peri- and postmenopausal symptoms were evaluated by a questionnaire and plasma levels of follicle stimulating hormone (FSH) were measured.

Results:

After adjusting for confounding factors, vasomotor symptoms remained a significant explanatory factor for the occurrence of PLMs (adj. OR 1.86, 95% CI 1.03 - 3.37). In women with PLM arousals, adjusted OR for vasomotor symptoms was 1.61, 95% CI 0.76 – 3.42. PLMs did not seem to affect HRQoL.

Conclusion:

We found that clinically-significant PLMs, but not PLM with arousals, were more common among women with vasomotor symptoms, even after controlling for confounding factors. Menopausal status per se, as evidenced by FSH in the postmenopausal range, was not associated with PLMs.

 

Keywords
Sleep, periodic linb movements, women, menopause, vasomotor symptoms
National Category
Obstetrics, Gynecology and Reproductive Medicine Neurology Psychiatry
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-204195 (URN)10.5664/jcsm.3348 (DOI)000334591500003 ()24426815 (PubMedID)
Available from: 2013-07-23 Created: 2013-07-23 Last updated: 2017-12-06Bibliographically approved
Wesström, J., Skalkidou, A., Manconi, M., Fulda, S. & Sundström Poromaa, I. (2014). Pre-pregnancy Restless Legs Syndrome (Willis-Ekbom Disease) Is Associated with Perinatal Depression. Journal of Clinical Sleep Medicine (JCSM), 10(5), 527-533
Open this publication in new window or tab >>Pre-pregnancy Restless Legs Syndrome (Willis-Ekbom Disease) Is Associated with Perinatal Depression
Show others...
2014 (English)In: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, Vol. 10, no 5, p. 527-533Article in journal (Refereed) Published
Abstract [en]

Objectives: Both restless legs syndrome ([RLS], also known as Willis-Ekbom Disease [WED]) and depression are common during pregnancy. However, no prior studies have assessed if pregnant women with RLS have an elevated risk of depression during and/or after pregnancy.

Methods: 1,428 women who were pregnant in gestational week 16-17 were asked to participate in a longitudinal survey. They were followed by web-based questionnaires in gestational week 17 and 32, and 6 weeks after delivery. Data were also retrieved from prenatal and birth records. Two different sets of criteria were used to examine the prevalence of RLS in the cohort (International Restless Legs Syndrome Society Group standard criteria and the later developed CH-RLSQ11 questionnaire). The latter questionnaire attempts to exclude those with common "mimics" of RLS.

Results: Adjusted odds ratio for depression in gestational week 17, 32, and postpartum week 6 in relation to pre-pregnancy RLS onset and moderate to severe symptom severity were 4.74 (2.30 - 9.76), 3.67 (1.85 - 7.28), and 2.58 (1.28 - 5.21), respectively. No significant associations were seen in pregnant women with de novo RLS during pregnancy. When using the standard diagnostic RLS criteria and frequency of symptoms more than 2-3 days per week, the prevalence of RLS was 12.3%. With the CH-RLSQ11 questionnaire and the same threshold for frequency of symptoms the prevalence was 6.5%.

Conclusion: Women with RLS onset before pregnancy with moderate or severe symptoms had an increased risk of both antenatal and postnatal depression. The self-reported prevalence of RLS during pregnancy is lower when a questionnaire dealing with "mimics" is used.

Keywords
Restless legs syndrome, pregnancy, depression
National Category
Obstetrics, Gynecology and Reproductive Medicine Neurology Psychiatry
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-204150 (URN)10.5664/jcsm.3704 (DOI)000341135100011 ()
Available from: 2013-07-23 Created: 2013-07-22 Last updated: 2017-12-06Bibliographically approved
Wesström, J. (2013). Sleep Related Movement Disorders: Association with Menopause and Pregnancy. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Sleep Related Movement Disorders: Association with Menopause and Pregnancy
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

It is known that sleep problems affect people’s wellbeing and has great consequences for public health.

Restless legs syndrome (RLS) gives uncomfortable sensations in the legs at rest, leading to an irresistible need for activity. It aggravates in evening and at night. Therefore, RLS provides poorer sleep and can affect quality of life through fatigue, family life and social activities, work, and comorbidity. It is demonstrated a dysfunction of the dopaminergic system in the brain with low levels of dopamine and / or less sensitive dopamine receptors. RLS is more common in women and the prevalence increases with age and during pregnancy.

Periodic limb movements are characterized by uncontrolled stretching movements of the legs, especially the toes, ankles, knees and hips during sleep. They last between 0.5 and 5 seconds, and can cause brief awakenings leading to daytime sleepiness. The clinical significance of PLM is rather controversial and PLM is sometimes seen in healthy people with no daytime symptoms.

RLS is a subjective diagnosis and translated with the help of questionnaires. PLM however, can objectively be evaluated by polysomnography.

Depression is common during and after pregnancy. It is not known whether women with RLS during pregnancy have a higher risk of prenatal or postpartum depression.

The aims of this thesis was to  to examine the prevalence, associated symptoms and comorbidities, in particular, vasomotor symptoms, menopause, and hormone replacement therapy (HRT) use, among women who suffer from RLS and PLMs. We also evaluated the impact of RLS and PLMs on health related quality of life (HRQoL), and if RLS before and during pregnancy increases the risk of antenatal or postpartum depressive symptoms.

Three different poulations were used.  Paper 1-3 were cross-sectional and included 5000 resp. 10000 randomly selected women from the general populations of Dalarna and Uppsala County. Questionnaires, polysomnographic recordings, blodtests etc. were used. Paper 4 was a longitudinal cohort study where 1428 pregnant women in Uppsala County were followed.

In summary, data included in this thesis points out that RLS and PLMs are more common in women with estrogendeficiency-related symptoms of menopause. RLS-positive women had an impaired mental HRQoL compared to RLS-negative women and more often suffered from comorbidities. Data also revealed that women with RLS before and during pregnancy are at increased risk for depression during and after pregnancy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. p. 74
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 915
Keywords
Sleep, Restless Legs Syndrome, Women, Menopause, Pregnancy, Depression
National Category
Other Clinical Medicine
Research subject
Medicine
Identifiers
urn:nbn:se:uu:diva-204149 (URN)978-91-554-8703-4 (ISBN)
Public defence
2013-09-06, Gustavianum, Akademigatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2013-08-16 Created: 2013-07-22 Last updated: 2014-01-07Bibliographically approved
Manconi, M., Ulfberg, J., Berger, K., Ghorayeb, I., Wesström, J., Fulda, S., . . . Pollmacher, T. (2012). When gender matters : Restless legs syndrome: Report of the "RLS and woman" workshop endorsed by the European RLS Study Group. Sleep Medicine Reviews, 16(4), 297-307
Open this publication in new window or tab >>When gender matters : Restless legs syndrome: Report of the "RLS and woman" workshop endorsed by the European RLS Study Group
Show others...
2012 (English)In: Sleep Medicine Reviews, ISSN 1087-0792, E-ISSN 1532-2955, Vol. 16, no 4, p. 297-307Article, review/survey (Refereed) Published
Abstract [en]

Sleep is an essential human behavior that shows prominent gender differences. Disturbed sleep, in particular, is much more prevalent in females than males. Restless legs syndrome (RLS) as one cause of disturbed sleep was observed to be somewhat more common among women than men in Ekbom's 1945 seminal series of clinical cases with the disease. He, however, reported this gender difference mainly for those with more severe symptoms. Since then numerous studies have reported that women are affected by RLS about twice as often as males for mild as well as moderate to severe RLS. The present review focuses on RLS in females from the perspectives of both epidemiology and pathophysiology. RLS will generally become worse or might appear for the first time during pregnancy. Parity increases the risk of RLS later in life suggesting that pregnancy is a specific behavioral risk factor for developing RLS. Some evidence suggests that dysfunction in iron metabolism and high estrogen levels might contribute to RLS during pregnancy. But, menopause does not lower the incidence of RLS nor does hormone replacement therapy lead to an increase, suggesting a quite complex uncertain role of hormones in the pathophysiology of RLS. Therefore, further, preferably longitudinal studies are needed to unravel the factors causing RLS in women. These studies should include genetic, clinical and polysomnographic variables, as well as hormonal measures and variables assessing iron metabolism.

Keywords
Restless legs syndrome, Gender, Female, Sleep, Insomnia, Pregnancy, Estrogens, Menopause, Quality of life
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-178184 (URN)10.1016/j.smrv.2011.08.006 (DOI)000306096700003 ()
Available from: 2012-07-31 Created: 2012-07-30 Last updated: 2017-12-07Bibliographically approved
Wesström, J., Ulfberg, J. & Nilsson, S. (2005). Sleep apnea and hormone replacement therapy: a pilot study and a literature review. Acta Obstetricia et Gynecologica Scandinavica, 84(1), 54-57
Open this publication in new window or tab >>Sleep apnea and hormone replacement therapy: a pilot study and a literature review
2005 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 84, no 1, p. 54-57Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Sleep apnea syndrome (SAS) is a common condition and a risk factor of cardiovascular and cerebrovascular diseases. The purpose of this pilot study was to investigate the effect of a gestagen (trimegeston) and estradiol hormone combination on perimenopausal and postmenopausal women with SAS.

METHODS:

Four postmenopausal and one perimenopausal women were studied by polysomnography before and after treatment with hormone replacement therapy (HRT).

RESULTS:

The subjects had a mean reduction of the severity of their sleep apnea by 75% measured by apnea/hypopnea index.

CONCLUSIONS:

HRT might be an alternative in the treatment of SAS.

National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-203465 (URN)10.1111/j.0001-6349.2005.00575.x (DOI)15603568 (PubMedID)
Available from: 2013-07-11 Created: 2013-07-11 Last updated: 2017-12-06Bibliographically approved
Organisations

Search in DiVA

Show all publications