MN1 C-terminal truncation syndrome is a novel neurodevelopmental and craniofacial disorder with partial rhombencephalosynapsis.

MN1 encodes a transcriptional co-regulator without homology to other proteins, previously implicated in acute myeloid leukaemia and development of the palate. Large deletions encompassing MN1 have been reported in individuals with variable neurodevelopmental anomalies and non-specific facial features. We identified a cluster of de novo truncating mutations in MN1 in a cohort of 23 individuals with strikingly similar dysmorphic facial features, especially midface hypoplasia, and intellectual disability with severe expressive language delay. Imaging revealed an atypical form of rhombencephalosynapsis, a distinctive brain malformation characterized by partial or complete loss of the cerebellar vermis with fusion of the cerebellar hemispheres, in 8/10 individuals. Rhombencephalosynapsis has no previously known definitive genetic or environmental causes. Other frequent features included perisylvian polymicrogyria, abnormal posterior clinoid processes and persistent trigeminal artery. MN1 is encoded by only two exons. All mutations, including the recurrent variant p.Arg1295* observed in 8/21 probands, fall in the terminal exon or the extreme 3' region of exon 1, and are therefore predicted to result in escape from nonsense-mediated mRNA decay. This was confirmed in fibroblasts from three individuals. We propose that the condition described here, MN1 C-terminal truncation (MCTT) syndrome, is not due to MN1 haploinsufficiency but rather is the result of dominantly acting C-terminally truncated MN1 protein. Our data show that MN1 plays a critical role in human craniofacial and brain development, and opens the door to understanding the biological mechanisms underlying rhombencephalosynapsis.

Genetic variants in the KDM6B gene are associated with neurodevelopmental delays and dysmorphic features.

Lysine-specific demethylase 6B (KDM6B) demethylates trimethylated lysine-27 on histone H3. The methylation and demethylation of histone proteins affects gene expression during development. Pathogenic alterations in histone lysine methylation and demethylation genes have been associated with multiple neurodevelopmental disorders. We have identified a number of de novo alterations in the KDM6B gene via whole exome sequencing (WES) in a cohort of 12 unrelated patients with developmental delay, intellectual disability, dysmorphic facial features, and other clinical findings. Our findings will allow for further investigation in to the role of the KDM6B gene in human neurodevelopmental disorders.

Socio-Demographic Variables and Successful Aging of the Angolan Elderly.

The proportion of elderly people is growing faster than any other age group. Amongst them, the group of oldest old is indeed the segment of the elderly population with the fastest growth rate. The increase in the proportion of elderly in the Angolan population makes research on this area badly needed. Within the theoretical framework of successful aging, the study aims to test for sociodemographic group differences in perceived health, life satisfaction, and social relations in Angolan elderly. The dependent variables are three of the components of what has been called successful aging. Data came from a cross-sectional survey of elderly people living in Luanda. 1003 Angolan elderly were surveyed on sociodemographic information, perceived health, life satisfaction, and social support. MANOVAs were calculated to test for mean differences in the dependent variables. Results permit to conclude that the factors associated with the largest differences on the Angolan elderly's quality of life and social relations were age (becoming oldest old) and institutionalization. The interactions of several factors with age pointed out that the oldest old were clearly a group in which the decreased quality of life due to becoming oldest old could not be compensated by other factors, as it was the case in the group of young old.