NHLRC2 variants identified in patients with fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) : characterisation of a novel cerebropulmonary disease

A novel multi-organ disease that is fatal in early childhood was identified in three patients from two non-consanguineous families. These children were born asymptomatic but at the age of 2 months they manifested progressive multi-organ symptoms resembling no previously known disease. The main clinical features included progressive cerebropulmonary symptoms, malabsorption, progressive growth failure, recurrent infections, chronic haemolytic anaemia and transient liver dysfunction. In the affected children, neuropathology revealed increased angiomatosis-like leptomeningeal, cortical and superficial white matter vascularisation and congestion, vacuolar degeneration and myelin loss in white matter, as well as neuronal degeneration. Interstitial fibrosis and previously undescribed granuloma-like lesions were observed in the lungs. Hepatomegaly, steatosis and collagen accumulation were detected in the liver. A whole-exome sequencing of the two unrelated families with the affected children revealed the transmission of two heterozygous variants in the NHL repeat-containing protein 2 (NHLRC2); an amino acid substitution p.Asp148Tyr and a frameshift 2-bp deletion p.Arg201GlyfsTer6. NHLRC2 is highly conserved and expressed in multiple organs and its function is unknown. It contains a thioredoxin-like domain; however, an insulin turbidity assay on human recombinant NHLRC2 showed no thioredoxin activity. In patient-derived fibroblasts, NHLRC2 levels were low, and only p.Asp148Tyr was expressed. Therefore, the allele with the frameshift deletion is likely non-functional. Development of the Nhlrc2 null mouse strain stalled before the morula stage. Morpholino knockdown of nhlrc2 in zebrafish embryos affected the integrity of cells in the midbrain region. This is the first description of a fatal, early-onset disease; we have named it FINCA disease based on the combination of pathological features that include fibrosis, neurodegeneration, and cerebral angiomatosis.Peer reviewe

Birch (Betula spp.) wood biochar is a potential soil amendment to reduce glyphosate leaching in agricultural soils

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Pyrolyysilämpötila vaikuttaa biohiilen kykyyn vähentää glyfosaatin huuhtoutumista peltomaasta

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Development and behaviour of 5-year-old very low birthweight infants

The place and time of birth influence the mortality of premature infants. We studied the effect of prematurity, time of birth, birth hospital level and district on the development and behaviour in a national cohort of 5-year-old Finnish very low birthweight infants (VLBWI). All surviving VLBWI (gestational age <32 weeks or birthweight ≤1,500 g) born in 2001–2002 in level II or III hospitals in Finland and full-term controls were included. The parents of 588 (64%) VLBWI and 176 (46%) controls returned the Five to Fifteen questionnaire (FTF) on the development and behaviour of their 5-year-old children. The questionnaire scores were linked to data from the National Medical Birth Register, the Hospital Discharge Register, the Register of Congenital Malformations and the Cause of Death Register. VLBWI had lower developmental and behavioural scores compared to the controls in all FTF domains. In VLBWI, the scores were less optimal, the lower the gestational age was. The time of birth, birth hospital level and district were not associated with the developmental and behavioural scores in VLBWI. In conclusion, short duration of pregnancy adversely influences development and behaviour in VLBWI. Despite differences previously demonstrated in mortality related to time and place of birth, there were no differences in developmental and behavioural scores in VLBWI according to the time of birth, birth hospital level or district. Thus, the survival advantage in level III hospitals seems not to be gained at the expense of behavioural or developmental problems