Weaver syndrome (WS) is a rare congenital disorder characterized by generalized overgrowth, macrocephaly, specific facial features, accelerated bone age, intellectual disability, and susceptibility to cancers. De novo mutations in the enhancer of zeste homolog 2 (EZH2) have been shown to cause WS. EZH2 is a histone methyltransferase that acts as the catalytic agent of the polycomb‐repressive complex 2 (PRC2) to maintain gene repression via methylation of lysine 27 on histone H3 (H3K27). Functional studies investigating histone methyltransferase activity of mutant EZH2 from various cancers have been reported, whereas WS‐associated mutations remain poorly characterized. To investigate the role of EZH2 in WS, we performed functional studies using artificially assembled PRC2 complexes containing mutagenized human EZH2 that reflected the codon changes predicted from patients with WS. We found that WS‐associated amino acid alterations reduce the histone methyltransferase function of EZH2 in this in vitro assay. Our results support the hypothesis that WS is caused by constitutional mutations in EZH2 that alter the histone methyltransferase function of PRC2. However, histone methyltransferase activities of different EZH2 variants do not appear to correlate directly with the phenotypic variability between WS patients and individuals with a common c.553G>C (p.Asp185His) polymorphism in EZH2.

Background:Current interventions in amyotrophic lateral sclerosis (ALS) are focused on supporting quality of life (QoL) and easing pain with a multidisciplinary approach.Objective:Primary aim of this pilot work assessed feasibility, safety, tolerability and satisfaction of osteopathic manual treatment (OMT) in 14 ALS outpatients.Methods:Patients were randomized according to an initial single-blind design (12 weeks, T0-T1), in order to receive OMT (weekly for 4 weeks, and fortnightly for the following 8 weeks) versus usual-care (n=7 each group), followed by an OMT open period (T1-T2, once a week for 8 weeks, n=10). Secondary aims included blind osteopathic assessment of somatic dysfunctions (SD) for goal attainment scale (GAS) calculation, Brief Pain Inventory-short form and McGill QoL-16 items.Results:OMT was demonstrated feasible and safe and patients displayed high satisfaction (T1-VAS=8.34 ± 0.46; T2-VAS=8.52 ± 0.60). Considering secondary aims no significant differences emerged. Finally, at study entry (T0), a cervico-dorsal SD was found in 78% of ALS patients versus 28% of healthy matched controls (p<0.01).Conclusion:OMT was found feasible, safe and satisfactory in ALS. The lack of secondary aim differences can be due to the limited sample size. OMT could be an interesting option to explore in ALS.

During a 5-year-period, 17 cases of congenital adenomatoid malformation of the lung were observed in the Department of Pediatric Surgery of Bologna University-S. Orsola-Malpighi Hospital; 16 cases were diagnosed in utero by ultra-sound. 13 patients had prenatal diagnosis between 21 and 23 weeks of gestation; 2 cases were diagnosed at 25 weeks and another one at 26 weeks. The other case came from another hospital, and the diagnosis was accidentally detected postnatally. In 3 cases the parents decided to terminate the pregnancy 3 cases had spontaneous improvement during the last weeks of gestation, and were perfectly normal at birth. One case was lost to follow-up; all remaining patients underwent resection. Among these patients only one was a nonsurvivor, while 9 have completely recovered. However, one patient developed persistent pulmonary hypertension, which could successfully be treated with drugs, another underwent laser treatment for laryngeal stenosis due to intubation. A special epidemiological information: 13 out 17 cases (76.5%) were female.

We describe a family in which four individuals (the mother and three children) presented with an overlapping phenotype of minor physical anomalies and intellectual disability. Four previously unreported copy number variants were found inherited either from the affected mother or from the healthy father, consisting of a 3p22.3p22.2 deletion (2.5 Mb), a 3p24.3 deletion (0.55 Mb), a 6q22.31 duplication (0.74 Mb), all maternally inherited, and an 18q11.2 duplication (0.276 Mb) which was paternally inherited. The deletions on chromosome 3 were both found to segregate with the disease. However, being the 0.55 Mb deleted segment on 3p24.3 devoid of genes, we considered that the 2.5 Mb deletion on 3p22.3p22.2 acts as major pathogenic rearrangement in this condition. Among the transcribed genes residing in this interval, ARPP21 and CLASP2 are proposed as good candidate genes on the basis of their functional properties. A co-morbidity role for the other small rearrangements detected in the affected individuals in association with the 3p22.3p22.2 deletion is also suggested, according to a second-side model of pathogenesis.