Identification of C12orf4 as a gene for autosomal recessive intellectual disability.

Intellectual disability (ID) is a major health problem in our society. Genetic causes of ID remain unknown because of its vast heterogeneity. Here we report two Finnish families and one Dutch family with affected individuals presenting with mild to moderate ID, neuropsychiatric symptoms and delayed speech development. By utilizing whole exome sequencing (WES), we identified a founder missense variant c.983T>C (p.Leu328Pro) in seven affected individuals from two Finnish consanguineous families and a deletion c.799_1034-429delinsTTATGA (p.Gln267fs) in one affected individual from a consanguineous Dutch family in the C12orf4 gene on chromosome 12. Both the variants co-segregated in the respective families as an autosomal recessive trait. Screening of the p.Leu328Pro variant showed enrichment in the North Eastern sub-isolate of Finland among anonymous local blood donors with a carrier frequency of 1:53, similar to other disease mutations with a founder effect in that region. To date, only one Arab family with a three affected individuals with a frameshift insertion variant in C12orf4 has been reported. In summary, we expand and establish the clinical and mutational spectrum of C12orf4 variants. Our findings implicate C12orf4 as a causative gene for autosomal recessive ID.

Nutrient dynamics in small mesotrophic fens surrounded by cultivated land : II. N and P accumulation in plant biomass in relation to the release of inorganic N and P in the peat soil.

Release of inorganic N and P in the organic soils of three small quaking fens in The Netherlands was studied by means of in situ incubation of the peat soil in plastic bottles. One of the fens had higher biomass production and lower species richness than the other two. The former fen is located in an area with downward groundwater percolation, whereas the latter fens are situated in an area of upward seepage of groundwater rich in calcium and bicarbonate.Mineralization of N proved to be slow in the low-productive fens, and 6 times faster in the highly productive fen. In the latter fen the amount of N mineralized during a certain period exceeded by far the amount accumulated in that period in the above-ground parts of the vegetation.The release of inorganic P was extremely slow in the two low-productive fens and rapid in the highly productive fen. The release rates were not related to the total P content of the soils. The slow P release in the low-productive fens may be due to the continuous inflow of groundwater rich in Ca, Al and Fe compounds.It can be concluded that the soil is a potentially large source of inorganic N and P in quaking fens. The importance of the soil versus other N and P sources is greater in nutrient-rich fens.