Variable clinical expression of Stickler Syndrome: A case report of a novel COL11A1 mutation

Background: Stickler Syndrome is a rare connective tissue disorder, characterized by clinical, and genetic heterogeneity. The clinical expression is highly variable, including moderate to severe myopia in childhood, hearing loss, facial dysmorphic features, cleft palate, and early osteoarthritis. COL2A1, COL11A1, and COL11A2 mutations account of the majority of autosomal dominant Stickler Syndrome and, in particular, a heterozygous mutation in COL11A1 gene is identified in about 10 to 20% of Stickler Syndrome patients. Methods: Herein, we report a case of an 8-year- old child with Stickler Syndrome, presenting with early-onset of myopia with vitreal abnormalities, facial dysmorphic characteristics, and mild hearing loss later in childhood. To identify the underlying genetic cause, Whole Exome Sequencing was carried out for COL11A1 gene. Results: A novel de novo heterozygous splice site variant (NM_001854: c.1845 + 5G> C) of the COL11A1 gene, which had not been previously reported, was identified by Whole Exome Sequencing. Conclusion: We reported a novel COL11A1 mutation in a child with Stickler Syndrome presenting a phenotype of early-onset of ocular anomalies and mild hearing loss later in childhood. Our findings confirm the variability of the expression of the disease, even in the contest of the same gene-related disorder, thus, contributing to improve the knowledge on clinical and molecular basis of this rare disease

Secondary peripheral chondrosarcoma arising in solitary osteochondroma: variables influencing prognosis and survival

Background: Secondary peripheral chondrosarcomas arising in solitary osteochondromas is an unusual complication, reported in small series. In this study, we aimed to present our experience with this rare variant of chondrosarcoma and compare results with already published data in order to determine prognostic factors for overall and disease-free survival. Methods: The case study includes retrospective data from patients diagnosed at a single institution from 1943 to 2019. Clinical data were collected reviewing all available medical records from first to last follow-up visits. To exclude the presence of the Multiple Osteochondroma Hereditary Syndrome, few patients, with a suspect of a familial form of the disease, were evaluated for the presence of germline heterozygous variants in EXT1 and EXT2 genes. Results were summarized using descriptive statistics and statistical analysis were performed to reveal associations between variables. Results: Two hundred and fourteen secondary peripheral chondrosarcomas that arose exclusively from solitary osteochondromas diagnosed in a multidisciplinary setting at the IRCCS Istituto Ortopedico Rizzoli were retrospectively identified, 66.4% males and 33.6% females with a median age at diagnosis of 38 years. The local recurrence rate was 17.3%, while the metastases one was 5.1%. Besides age, a high histologic grade is the only factor associated with worse 5-year and 10-year overall survival (log-rank p = 0.0005, HR = 3.74; 95% CI 1.69–8.26). Moreover, high histological grade (HR = 3.75; 95% CI = 1.69–8.34; p = 0.001) and surgical debulking (HR = 3.71; 95% CI = 1.57–8.79; p = 0.003) were associated with a significantly worse disease-free survival. Conclusions: Our study confirm the low-grade behavior of secondary peripheral chondrosarcomas and demonstrate that the best choice of treatment for those arising in solitary osteochondromas is the wide surgical excision, when possible. Location per se is not a factor that affects prognosis, while the accurate histological grade assessment is correlated with the tumor aggressiveness and a long term follow up is necessary for this rare variant of chondrosarcoma

Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series

Melorheostosis (MEL) is an uncommon, sclerosing disease, characterised by hyperostosis of long bones, resembling the flowing of candle wax. The disease is sporadic and the pathogenesis is still poorly understood. Occasionally, the same family can include individuals with MEL and Osteopoikilosis (OPK), a disease characterised by multiple round foci of increased bone density. LEMD3 gene mutations are related to OPK and Buschke\u2013Ollendorff Syndrome, a genetic condition in which an association between MEL, OPK and skin lesions is observed. In rare cases, LEMD3 mutations and recently mosaic MAP2K1 gene mutations have been correlated to MEL suggesting that somatic mosaicism could be causative of the disease. In this study, we described the clinical, radiological and molecular findings of 19 individuals with MEL and 8 with OPK and compared the results to the medical literature. The molecular analyses of this case series corroborate the available data in the medical literature, indicating that LEMD3 germline mutations are not a major cause of isolated MEL and reporting five further cases of OPK caused by LEMD3 germline mutations

Chiral Anomaly and CPT invariance in an implicit momentum space regularization framework

This is the second in a series of two contributions in which we set out to establish a novel momentum space framework to treat field theoretical infinities in perturbative calculations when parity-violating objects occur. Since no analytic continuation on the space-time dimension is effected, this framework can be particularly useful to treat dimension-specific theories. Moreover arbitrary local terms stemming from the underlying infinities of the model can be properly parametrized. We (re)analyse the undeterminacy of the radiatively generated CPT violating Chern-Simons term within an extended version of $QED_4$ and calculate the Adler-Bardeen-Bell-Jackiw triangle anomaly to show that our framework is consistent and general to handle the subtleties involved when a radiative corretion is finite.Comment: 16 pages, LaTeX, version to appear in PR

Providing high-quality care remotely to patients with rare bone diseases during COVID-19 pandemic

During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the "COVID-19 Helpline for Rare Bone Diseases" in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the "COVID-19 Helpline for Rare Bone Diseases" launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients' care

Purificação de um Potyvirus de ocorrência natural em Hypochaeris brasiliensis.

O gênero Potyvirus é responsável por causar a maior parte das viroses em plantas. Esses vírus têm forma de partículas flexuosas, apresentando de 11 nm a 15 nm de largura e 680 nm a 900 nm de comprimento e constituídos por RNA, fita simples e senso positivo. Hypochaeris brasiliensis é uma planta daninha encontrada na cultura da soja. O objetivo deste trabalho foi a obtenção de uma suspensão viral para a produção de antissoro e o estudo dos componentes estruturais do vírus. Inicialmente, coletou-se 100 g de folhas com sintomas que foram macerados na presença de tampão fosfato de sódio 0,2 M, pH 7. Posteriormente utilizou-se 8,5% de butanol e submeteu-se a centrifugações diferenciais, sendo a primeira ultracentrifugação com colchão de sacarose 20%. A massa molecular da proteína capsidial, foi determinada por eletroforese em gel de poliacrilamida (SDS-PAGE). Para cada 100 g de folha, obteve-se 600 µL de suspensão de vírus purificado. A relação de absorbância entre 260 nm e 280 nm foi de 1,38 e as amostras referentes à proteína do capsídeo do vírus apresentaram massa molecular de 34 kDa. O coeficiente de extinção utilizado foi de 2,3, concluindo-se que 100 g de tecido infectado de H. brasiliensis tinha ao final 1 mg de vírus ml-1 . Esse método apresentou uma quantidade satisfatória de suspensão de vírus purificado. Com base na massa molecular da proteína capsidial, e das inclusões citoplasmáticas tipo catavento, concluiu-se que o mesmo pertence ao gênero Potyvirus

Consistency Relations for an Implicit n-dimensional Regularization Scheme

We extend an implicit regularization scheme to be applicable in the $n$-dimensional space-time. Within this scheme divergences involving parity violating objects can be consistently treated without recoursing to dimensional continuation. Special attention is paid to differences between integrals of the same degree of divergence, typical of one loop calculations, which are in principle undetermined. We show how to use symmetries in order to fix these quantities consistently. We illustrate with examples in which regularization plays a delicate role in order to both corroborate and elucidate the results in the literature for the case of CPT violation in extended $QED_4$, topological mass generation in 3-dimensional gauge theories and the Schwinger Model and its chiral version.Comment: 21 pages, LaTeX, to appear in Phys.Rev.