http://repub.eur.nl/res/aut/32840/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37368/ 2012-10-01T00:00:00Z A 101/2-year-old boy was born at full term, the second child of nonconsanguineous parents. Pregnancy and parturition were uncomplicated. Breast feeding was complicated because of nasal regurgitation. He developed a positional plagiocephaly, and had a inguinal hernia and right-sided cryptorchidism, which were both corrected when he was 9 weeks old. Because of poor movements at the age of 4 months, physiotherapy was started and he was examined by a neurologist. Facial dysmorphisms (epicanthus, hypertelorism, down-slanted palpebral fissures, ptosis, small right orbit, low-set ears and webbed neck), pectus excavatum with a wide internipple distance, head lag, poverty of movement and plagiocephaly were present. At 8 months, a delayed development with a tonic dysregulation was noted. Fine motor, adaptive and personal social behaviour were adequate. At the age of 34 months, speech therapy showed a language and speech development delay of, respectively, 4 and 10 months. http://repub.eur.nl/res/pub/24902/ 2009-09-01T00:00:00Z Background: The 9q subtelomeric deletion syndrome (9qSTDS) is clinically characterised by moderate to severe mental retardation, childhood hypotonia and facial dysmorphisms. In addition, congenital heart defects, urogenital defects, epilepsy and behavioural problems are frequently observed. The syndrome can be either caused by a submicroscopic 9q34.3 deletion or by intragenic EHMT1 mutations leading to haploinsufficiency of the EHMT1 gene. So far it has not been established if and to what extent other genes in the 9q34.3 region contribute to the phenotype observed in deletion cases. This study reports the largest cohort of 9qSTDS cases so far. Methods and results: By a multiplex ligation dependent probe amplification (MLPA) approach, the authors identified and characterised 16 novel submicroscopic 9q deletions. Direct sequence analysis of the EHMT1 gene in 24 patients exhibiting the 9qSTD phenotype without such deletion identified six patients with an intragenic EHMT1 mutation. Five of these mutations predict a premature termination codon whereas one mutation gives rise to an amino acid substitution in a conserved domain of the protein. Conclusions: The data do not provide any evidence for phenotype-genotype correlations between size of the deletions or type of mutations and severity of clinical features. Therefore, the authors confirm the EHMT1 gene to be the major determinant of the 9qSTDS phenotype. Interestingly, five of six patients who had reached adulthood had developed severe psychiatric pathology, which may indicate that EHMT1 haploinsufficiency is associated with neurodegeneration in addition to neurodevelopmental defect.