Early onset developmental and epileptic encephalopathy and Rett-like phenotype in a 15-year-old girl affected by Cornelia de Lange syndrome type 2 due to a SMC1A gene mutation.

Developmental and epileptic encephalopathies (DEE) are conditions in which a mutated gene may cause abnormal functioning of the central nervous system, resulting in both encephalopathy and epileptogenesis. We present a case of a girl with a DEE characterized by a Rett-like phenotype in association with febrile and afebrile clusters of focal seizures. The girl presented typical development until the age of 18 months, followed by regression. The first febrile bilateral tonic-clonic seizure was observed at 30 months of age, and the following month seizures recurred in clusters of several episodes per day every 10 days. These seizures were characterized by behavioural arrest, emotional symptoms, head turning, and followed by bilateral tonic-clonic seizures. The administration of valproic acid and levetiracetam led to prolonged seizure control. However, from the age of 7 years, she had monthly recurrent clusters of focal seizures and non-convulsive status epilepticus which occurred at different ages. Brain and spinal cord MRI showed mild non-progressive hemispheric cerebellar atrophy. A next generation sequencing panel for epilepsy identified the de novo splicing mutation c.2973+1G>A of the SMC1A gene.

pTNM stage distribution in breast cancer: a population-based survey in northern Italy. Collaborative Group of Pathologists for Cancer Registration in Verona.

AIMS AND BACKGROUND: The role of distribution by stage at diagnosis in breast cancer has been considered in many studies, with particular regard to evaluation of prognosis, impact of screening programs and quality of care. Nevertheless, international comparisons of descriptive data can be hampered by lack of homogeneity in staging methods. The TNM is presently the most common staging system used all over the world, although some criticism have been raised recently against its pragmatic value. The present study reports a population-based survey of pathologic TNM distribution in incident cases of female breast cancer in the Verona province, a geographical area of northern Italy covered by cancer registration. METHODS: All histologically proven incident cases of breast cancer were identified in the study period 1988-1990 and classified as for tumor size and nodal involvement according to the pathological TNM criteria. The type of surgical treatment was also registered for all cases diagnosed in 1990. RESULTS: one thousand two hundreds and fifty-four invasive and in situ breast cancers were observed and pT1 cases accounted for 44.4%. Nodal involvement was present in 41.5% of invasive cancers. A surgical treatment was performed in 1213 patients (96.7%). Axillary dissection was reported in 1080 cases, 820 of them (76.6%) having 10 or more lymph nodes examined. Radical mastectomy accounted for 74% of the 458 breast cancers diagnosed in 1990 and 31.6% of the eligible cases were conservatively treated. CONCLUSIONS: Cancer registries should be encouraged to report data on stage distribution in breast cancer (and in other malignancies). This practice could improve international comparisons and give an essential contribution to studies on survival, screening programs and quality of care.

Cancer registration: a feasibility study in northern Italy. The Collaborative Group of Pathologists for Cancer Registration in Verona.

A pilot study was carried out in the province of Verona, in the north-east of Italy, in order to assess the feasibility of establishing a population-based cancer registry in the area. The quality of routinely collected data, particularly histological diagnoses and hospital discharge codes, was evaluated for the year 1988. All the histologically confirmed incident cancers observed in the pathology departments of the study area were registered and compared to the expected cases. Moreover, computerised discharge codes were tested for accuracy in identifying hospitalised patients with cancer. Finally, the sensitivity of the two sources combined was measured (90.3%). This study could provide helpful information to cancer registries which intend to assess the quality of specific sources of data both for planning and periodical evaluation purposes.

Gly85 to Val substitution in pro alpha 1(I) chain causes mild osteogenesis imperfecta and introduces a susceptibility to protease digestion.

In this paper we describe a mild moderate form of osteogenesis imperfecta caused by a point mutation in COL1A1 which converted glycine 85 to valine. The valine substitution introduced into the triple-helical domain of type-I collagen a conformational perturbation causing susceptibility to digestive proteases. In fact, SDS/PAGE of pepsin-treated collagen showed the presence of a faint band, migrating between alpha 1(I) and alpha 2(I), both in the medium and in the cell layer. On trypsin digestion the band, a shortened form of alpha 1(I), had a melting temperature of 39.5 degrees C. If the triple-helical collagen was obtained after trypsin or chymotrypsin digestion of procollagen, two shortened bands were identified; the enzymes cleaved about 40% of the trimers. The mutant procollagen was normally secreted and processed in the extracellular matrix at a normal rate. When native type-I collagen was formed after dextran-sulfate incubation, only chains of normal length were found, suggesting that the fibroblast proteases did not recognize the alteration introduced by the mutation. The effects of glycine 85 to valine substitution are compared with those produced by a previously described arginine substitution of the same residue (Deak et al., 1991).