Burden of rare coding variants in an Italian cohort of familial multiple sclerosis.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative demyelinating disease of the central nervous system. It is a complex and heterogeneous disease caused by a combination of genetic and environmental factors, and it can cluster in families. OBJECTIVE: to evaluate at gene-level the aggregate contribution of predicted damaging low-frequency and rare variants to MS risk in multiplex families. METHODS: We performed whole exome sequencing (WES) in 28 multiplex MS families with at least 3 MS cases (81 affected and 42 unaffected relatives) and 38 unrelated healthy controls. A gene-based burden test was then performed, focusing on two sets of candidate genes: i) literature-driven selection and ii) data-driven selection. RESULTS: We identified 11 genes enriched with predicted damaging low-frequency and rare variants in MS compared to healthy individuals. Among them, UBR2 and DST were the two genes with the strongest enrichment (p = 5 × 10-4 and 3 × 10-4, respectively); interestingly enough the association signal in UBR2 is driven by rs62414610, which was present in 25% of analysed families. CONCLUSION: Despite limitations, this is one of the first studies evaluating the aggregate contribution of predicted damaging low-frequency and rare variants in MS families using WES data. A replication effort in independent cohorts is warranted to validate our findings and to evaluate the role of identified genes in MS pathogenesis.

A new radioguided procedure for localization and surgical treatment of neck node metastasis of papillary thyroid cancer.

AIM OF THE STUDY: We intended to use a radioguided technique for pre-operative localization of neck node recurrences in patients with papillary thyroid cancer (PTC) already submitted to thyroidectomy and radioiodine treatment. PATIENTS AND METHODS: We selected 20 patients affected by PTC with evidence of neck nodes recurrences at ultrasound examination. Our method has been derived from the Radioguided Occult Lesion Localization technique used for pre-operative localization of occult breast lesions. The technique involves the inoculation of human albumin macroaggregates labeled with radioactive technetium (0.4 mCi in a volume of 0.05 ml) directly in the suspicious lesion, under ultrasound guidance. The persistence of the radioactive tracer in the nodes is confirmed by a scintigraphy performed 2 h after injection. During surgery, a gamma detecting probe is used to locate the suspicious lesions as "hot spots". RESULTS: Fifty lymph-nodes were injected with the tracer. All radiolabeled lymph-nodes were located and removed during surgery. At histology, metastasis of PTC was confirmed in 38/50 (76%) lymph-nodes. At least one metastatic lymph-node per patient was removed. In 8/20 (40%) patients, reactive lymphoid hyperplasia was found in 12/50 (24%) lymph-nodes. CONCLUSIONS: This radioguided technique has been highly effective for localization and surgical treatment of suspicious lymph-node detected at neck ultrasound and may play a valuable role in case of node metastases of thyroid cancer that show no radioiodine uptake.

Prevention and cure of rhinogenous deafness at the Thermal Baths "Bagni delle Galleraie".

INTRODUCTION: Hearing is foundamental for human social life. Secretory Otitis Media (SOM) is the most important cause of trasmissive hypoacusis in early childhood. METHODS: The Department of Physiopathology, Experimental Medicine and Public Health of Siena University in collaboration with the Thermal Baths "Bagni delle Galleraie" proposed a prevention and cure campaign of rhinogenous deafness in June 2002 in some primary schools in the Colle val D'Elsa district. A sample of 87 children was involved in the study (average age of 5,64 +/- 1,41 years). On entering the thermal baths a questionnaire was administered to the parents, to point out possible risk factors. RESULTS: Among the 87 children, 28 cases of SOM and 21 cases of severe tubal disorder were found. Only 19 cases out of 49 were already known to the parents and only 28 joined the study and were examined for three years consecutively. DISCUSSION: Out of the 35 children examined in 2002, 28 returned to "The Galleraie" for the two following years. They repeated the thermal cure for two years as a preventive measure. At present they are not affected by SOM and during the winters suffered a lower number of infections in the primary airways and took less antibiotics. CONCLUSIONS: Our study focuses on infant school children because of their critical age for linguistic and social development. Early diagnosis and therapy prevent any negative social development.