Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland

The genetics of autosomal recessive intellectual disability (ARID) has mainly been studied in consanguineous families, however, founder populations may also be of interest to study intellectual disability (ID) and the contribution of ARID. Here, we used a genotype-driven approach to study the genetic landscape of ID in the founder population of Finland. A total of 39 families with syndromic and non-syndromic ID were analyzed using exome sequencing, which revealed a variant in a known ID gene in 27 families. Notably, 75% of these variants in known ID genes were de novo or suspected de novo (64% autosomal dominant; 11% X-linked) and 25% were inherited (14% autosomal recessive; 7% X-linked; and 4% autosomal dominant). A dual molecular diagnosis was suggested in two families (5%). Via additional analysis and molecular testing, we identified three cases with an abnormal molecular karyotype, including chr21q22.12q22.2 uniparental disomy with a mosaic interstitial 2.7 Mb deletion covering DYRK1A and KCNJ6. Overall, a pathogenic or likely pathogenic variant was identified in 64% (25/39) of the families. Last, we report an alternate inheritance model for 3 known ID genes (UBA7, DDX47, DHX58) and discuss potential candidate genes for ID, including SYPL1 and ERGIC3 with homozygous founder variants and de novo variants in POLR2F and DNAH3. In summary, similar to other European populations, de novo variants were the most common variants underlying ID in the studied Finnish population, with limited contribution of ARID to ID etiology, though mainly driven by founder and potential founder variation in the latter case.Peer reviewe

Exome sequencing reveals predominantly de novo variants in disorders with intellectual disability (ID) in the founder population of Finland

The genetics of autosomal recessive intellectual disability (ARID) has mainly been studied in consanguineous families, however, founder populations may also be of interest to study intellectual disability (ID) and the contribution of ARID. Here, we used a genotype-driven approach to study the genetic landscape of ID in the founder population of Finland. A total of 39 families with syndromic and non-syndromic ID were analyzed using exome sequencing, which revealed a variant in a known ID gene in 27 families. Notably, 75% of these variants in known ID genes were de novo or suspected de novo (64% autosomal dominant; 11% X-linked) and 25% were inherited (14% autosomal recessive; 7% X-linked; and 4% autosomal dominant). A dual molecular diagnosis was suggested in two families (5%). Via additional analysis and molecular testing, we identified three cases with an abnormal molecular karyotype, including chr21q22.12q22.2 uniparental disomy with a mosaic interstitial 2.7 Mb deletion covering DYRK1A and KCNJ6. Overall, a pathogenic or likely pathogenic variant was identified in 64% (25/39) of the families. Last, we report an alternate inheritance model for 3 known ID genes (UBA7, DDX47, DHX58) and discuss potential candidate genes for ID, including SYPL1 and ERGIC3 with homozygous founder variants and de novo variants in POLR2F and DNAH3. In summary, similar to other European populations, de novo variants were the most common variants underlying ID in the studied Finnish population, with limited contribution of ARID to ID etiology, though mainly driven by founder and potential founder variation in the latter case

Molecular understanding of sulphuric acid-amine particle nucleation in the atmosphere

4 pages 359-363 in the print version, additional 7 pages online.Peer reviewe

The effect of acid-base clustering and ions on the growth of atmospheric nano-particles

The growth of freshly formed aerosol particles can be the bottleneck in their survival to cloud condensation nuclei. It is therefore crucial to understand how particles grow in the atmosphere. Insufficient experimental data has impeded a profound understanding of nano-particle growth under atmospheric conditions. Here we study nano-particle growth in the CLOUD (Cosmics Leaving OUtdoors Droplets) chamber, starting from the formation of molecular clusters. We present measured growth rates at sub-3 nm sizes with different atmospherically relevant concentrations of sulphuric acid, water, ammonia and dimethylamine. We find that atmospheric ions and small acid-base clusters, which are not generally accounted for in the measurement of sulphuric acid vapour, can participate in the growth process, leading to enhanced growth rates. The availability of compounds capable of stabilizing sulphuric acid clusters governs the magnitude of these effects and thus the exact growth mechanism. We bring these observations into a coherent framework and discuss their significance in the atmosphere.Peer reviewe

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome

Purpose: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. Methods: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. Results: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. Conclusion: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome

Down syndrome, health and disability:a population-based case record and follow-up study

Abstract The present study surveyed medical problems and mental health in an unselected population-based series of people with Down syndrome (DS). All people with DS identified in the Intellectual Disability Service Register in the Kainuu region (n=138) were included, and their health and disability case records in the public services were analysed. The severity of intellectual disability was related to age, gender, and recorded medical problems. Adaptive behaviour changes were assessed among adults repeatedly during ten years using the Adaptive Behaviour Scale - Residential and Community, Part I. The study evaluated health surveillance and practices were compared to the national Current Care guidelines. Numerous medical problems and behavioural symptoms were recorded in this population. Surgical treatments were used extensively. The number of medical problems varied to a great degree among participants. Health problems were extensive from birth to old age. Many health concerns were age-related. The degree of intellectual disability related to visual and neurological impairments. Depression, and among participants in their forties and older, Alzheimer’s disease were the most common underlying reasons for changes in adaptive behaviour. A gradual functional decline and dementia affected many participants at a relatively early age. Visual acuity and hearing should be regularly monitored in all individuals with DS because of a high prevalence of visual impairment and hearing loss in this population. There was a general lack of evidence that the health care guidelines initiated five years ago were being followed. This suggests that possibilities to enhance health have not been optimally implemented. Therefore, further efforts are needed to diagnose and treat medical problems in people with DS.Tiivistelmä Tutkimuksessa kuvattiin todettujen terveysongelmien yleisyyttä ja terveysseurannasta annettujen suositusten toteutumista Downin oireyhtymässä. Nykyisin Kainuussa elävien Down -henkilöiden tietojen lisäksi alueella aiemmin asuneiden saatavissa olevat sairaus- ja huoltokertomustiedot analysoitiin (n=138). Kehitysvammaisuuden vaikeusasteen, iän, sukupuolen ja todettujen sairauksien yhteyksiä selvitettiin. Aikuisten ja ikääntyvien Down -henkilöiden toimintakykyä seurattiin kymmenen vuoden ajan käyttäen Adaptiivisen käyttäytymisen asteikkoa. Käypä hoito -suosituksen toteutumista terveysseurannan osalta arvioitiin. Down -henkilöillä oli todettu lukuisia terveysongelmia ja käytösoireita kaikissa ikäryhmissä. Kirurgisia hoitoja oli tehty paljon. Yksilölliset erot sairastavuudessa ja toimintakyvyssä olivat erittäin huomattavat. Monet terveysongelmista liittyivät tiettyyn ikään. Vaikeasti kehitysvammaisilla todettiin enemmän silmäsairauksia ja näön ongelmia sekä neurologisia sairauksia kuin lievästi tai keskivaikeasti kehitysvammaisilla. Masennus ja yli 40 vuoden ikäisillä Alzheimerin tauti olivat yleisimmät toimintakyvyn heikentymisen syyt. Toimintakykvyn heikentyminen alkoi usein 40 ikävuoden jälkeen ja moni sairastui suhteellisen nuorena dementiaan. Kaikkien Down -henkilöiden kuuloa ja näköä tulisi seurata säännöllisesti, koska kuulon alentuminen ja näön ongelmat ovat yleisiä ja jäävät usein toteamatta. Hoitosuositukset eivät toteutuneet ainakaan säännöllisen kuulon ja kilpirauhasen toiminnan seurannan osalta viiden vuoden kuluessa suositusten antamisesta. Terveysseurannan parempi toimeenpano terveyden edistämiseksi on mahdollista. Down henkilöiden sairauksien toteamisen ja hoidon kehittäminen vaatii edelleen työtä

Herukan lajikekokeet käytännön viljelmillä

Nimekkeen selvennys: Kokeiden perustaminen vuosina 1997- -1999 ja satovuosien 2000, 2001 ja 2002 tulokset.Mustaherukan lajikekokeet perustettiin käytännön marjaviljelmille syksyllä 1997. Mukaan valittiin 17 koelajiketta ja verrannelajikkeeksi Öjebyn . Mustaherukkakokeita oli yhteensä 16 marjatilalla maan eri osissa, pääasiassa kuitenkin perinteisillä herukantuotantoalueilla maan keski- ja itäosissa. Mukana oli kolme luomutilaa. Valkoherukkakokeet, joita oli kuudella marjatilalla, perustettiin pääosin keväällä 1999. Koelajikkeena oli ainoastaan ruotsalainen Vit Jätte -lajike, jota verrattiin Valkea Hollantilainen lajikkeen kantaan Valkea Suomalainen . Kullakin koetilalla oli verrannelajikkeen lisäksi vähintään kolme koelajiketta vierekkäisissä riveissä. Ilomantsin Marjaviinikoulun koekentällä olivat kuitenkin mukana lähes kaikki mustaherukan koelajikkeet. Kutakin lajiketta istutettiin normaalein istutusetäisyyksin 100-200 kappaletta. Koekasvustoja hoidettiin samalla viljelytekniikalla kuin koetilan muitakin herukkakasvustoja. Sadot poimittiin yleensä patukkamenetelmällä, mutta poiminnoissa käytettiin myös konekorjuuta ja käsin poimintaa. Tässä raportissa esitetään vuosien 2000, 2001 ja 2002 satotulokset sekä lajikkeittain että koeviljelmittäin eriteltyinä. Taulukoissa on myös mittauksiin perustuvia tuloksia marjapainoista ja havaintoja pensaiden kasvutavasta ja kasvukunnosta. Koelajikkeiden marjojen flavonoidi- ja C-vitamiinipitoisuuksista esitetään kolmen vuoden mittaustulokset ja tuloksia eräiden mustaherukkalajikkeiden aistinvaraisista arvioista sekä rasiaherukan kuluttajatestistä. Lisäksi raportissa on yhteenveto koekasvustojen herukanrataspunkin seurantatutkimuksesta, josta on myös kolmen satovuoden tulokset. Hankkeen tulosten perusteella marjojen pääasiallista käyttötarkoitusta on pidettävä viljelyominaisuuksien lisäksi keskeisenä kriteerinä lajikevalintoja tehtäessä. Verrannelajike Öjebyn on edelleen viljelykelpoinen lajike Suomen oloissa, vaikka monet koelajikkeet olivat satoisampia. Moniin käyttötarkoituksiin soveltuva Mortti menestyi kokeissa hyvin, ja sen sato kypsyy 1,5-2 viikkoa myöhemmin kuin Öjebynin sato. Myös Sunniva lajike sopii moneen käyttötarkoitukseen ja erityisesti Itä-Suomen olosuhteisiin. Tuoremarjakauppaan soveltuvat suurimarjaiset Intercontinental-, Ben Tron- ja Hedda lajikkeet, joista Ben Tron oli parhaan makuinen aistinvaraisissa testeissä. Yhden satokauden tulosten perusteella valkoherukka Vit Jätte oli kokeissa satoisampi ja suurempimarjainen kuin verrannelajike Valkea Hollantilainen. Tulosaineiston perusteella lajikkeiden C-vitamiini- ja flavonoidipitoisuudet ovat lajiketyypillisiä ominaisuuksia. Eniten C-vitamiinia oli lajikkeissa Ben Tirran, Ben Connan ja Binar ja eniten flavonoideja lajikkeissa Ben Tron, Binar ja Ben Alder.In 1997 black and white currant variety trials were established on twenty berry farms in different parts of Finland. Three of the farms were organic. 17 black currrant varieties were studied and compared to variety Öjebyn . In white currant trials, a new Swedish variety Vit Jätte was studied and compared to White Dutch variety. 100-200 plants per each cultivar were planted 50-70 cm spacing in the rows. Rows were 4 m apart. The berry farmers took care of trial plants using same cultivation techniques than on their berry fields. The berries were mostly picked with the baton method. Also the harvesting by machine or hand picking were used. In this report the results of yielding years 2000... 2002 are being presented; yields, berry weights, harvesting time and, e.g., observations of growing habits of each variety. Also the results of C-vitamin and flavonoid contents of tested varieties will be presented. In 2002, some of the trial varieties were analyzed for the intensities of sensory characteristics. In addition, some trial varieties with big berry size were in a consumer test to study the suitability of these varieties to the fresh market. According to the results, cv. Öjebyn can be still recommended for cultivation in Finnish conditions, although many of the trial varieties gave bigger yields than Öjebyn . Finnish variety Mortti succeeded well in the trials. It ripens 1.5... 2 weeks later than Öjebyn and can be used for many purposes. Also Sunniva seems to be suitable for many purposes and it succeeded well in the trials, especially in the Eastern part of Finland. Varieties with big berry size, such as Intercontinental , Ben Tron and Hedda , are suitable for the fresh market. Ben Tron was the most liked variety in the consumer test. C-vitamin content and flavonoid content of black currant berries were at high level when compared to other berries and fruits. Both C-vitamin content and flavonoid content varied between varieties.vokMyynti MTT tietopalvelutBlack and white currant variety trials on berry farm

Lower thoracic spine extension mobility is associated with higher intensity of thoracic spine pain

Objectives: To evaluate the association of thoracic spine (TS) posture and mobility with TS pain. Methods: Participants with TS pain reported maximum, average, and night pain in TS area, and pain summary score was calculated. Upright and sitting TS postures were evaluated by inspection. TS posture and mobility (flexion and extension) were recorded using an inclinometer and a tape measure, respectively. Correlations between posture and mobility assessments were calculated using Spearman rank correlation, the association of TS posture and mobility with TS pain by logistic regression analysis. Results: The participants’ (n = 73, 52 females, age range 22–56) TS pain duration was 12 weeks on average. The correlations for measurements of TS posture and flexion mobility were higher than correlations of other TS measurements being between 0.53 and 0.82. Decreased extension mobility of the upper (from 1st to 6th TS segments; Th1–Th6) TS was associated with higher worst pain (OR 1.04, 95% CI 1.00–1.07) and whole TS with pain sum score (OR 1.05, 95% CI 1.01– 1.08). Less kyphotic whole TS was associated with lower pain sum score (OR 0.96, 95% CI 0.92– 1.00). Greater flexion mobility of upper and lower (Th6–Th12) TS were associated with lower pain sum score (OR 0.96, 95% CI 0.91–1.00, and OR 0.96, 95% CI 0.91–1.00, respectively). Conclusions: Reduced thoracic extension mobility was associated with higher pain scores and the greater flexion mobility with lower pain scores. Future research is warranted to evaluate if treatments geared toward TS extension mobility improvements would result in lower TS pain.peerReviewe

Development of Participation in and Identification With School : Associations With Truancy

This longitudinal study covering two educational transitions examined 1,821 Finnish students’ participation in and identification with school and their associations with students’ academic achievement and truancy. The students were surveyed (a) at the end of primary school, (b) at the beginning of lower secondary school, (c) at the end of lower secondary school, and (d) in the first year of upper secondary education. In alignment with the participation-identification model, higher levels of participation in school activities at the end of primary school predicted higher levels of identification (i.e., feelings of belonging and valuing school) at the end of lower secondary school. This association was mediated by academic achievement. High levels of both participation and identification at the end of lower secondary school predicted lower levels of truancy in upper secondary education. The study indicates that promoting students’ participation and identification during comprehensive school prevents student disengagement from upper secondary education.peerReviewe