@article {3602, title = {Clinical features and follow-up in patients with 22q11.2 deletion syndrome.}, journal = {J Pediatr}, volume = {164}, year = {2014}, month = {2014 Jun}, pages = {1475-80.e2}, abstract = {

OBJECTIVE: To investigate the clinical manifestations at diagnosis and during follow-up in patients with 22q11.2 deletion syndrome to better define the natural history of the disease.

STUDY DESIGN: A retrospective and prospective multicenter study was conducted with 228 patients in the context of the Italian Network for Primary Immunodeficiencies. Clinical diagnosis was confirmed by cytogenetic or molecular analysis.

RESULTS: The cohort consisted of 112 males and 116 females; median age at diagnosis was 4 months (range 0 to 36 years 10 months). The diagnosis was made before 2 years of age in 71\% of patients, predominantly related to the presence of heart anomalies and neonatal hypocalcemia. In patients diagnosed after 2 years of age, clinical features such as speech and language impairment, developmental delay, minor cardiac defects, recurrent infections, and facial features were the main elements leading to diagnosis. During follow-up (available for 172 patients), the frequency of autoimmune manifestations (P = .015) and speech disorders (P = .002) increased. After a median follow-up of 43 months, the survival probability was 0.92 at 15 years from diagnosis.

CONCLUSIONS: Our data show a delay in the diagnosis of 22q11.2 deletion syndrome with noncardiac symptoms. This study provides guidelines for pediatricians and specialists for early identification of cases that can be confirmed by genetic testing, which would permit the provision of appropriate clinical management.

}, keywords = {Abnormalities, Multiple, Adolescent, Adult, Age Factors, Child, Child, Preschool, Chromosomes, Human, Pair 22, Delayed Diagnosis, Developmental Disabilities, DiGeorge Syndrome, Disease Progression, Early Diagnosis, Female, Follow-Up Studies, Genetic Testing, Humans, Infant, Infant, Newborn, Male, Monitoring, Physiologic, Prospective Studies, Retrospective Studies, Risk Assessment, Severity of Illness Index, Sex Factors, Time Factors, Young Adult}, issn = {1097-6833}, doi = {10.1016/j.jpeds.2014.01.056}, author = {Cancrini, Caterina and Puliafito, Pamela and Digilio, Maria Cristina and Soresina, Annarosa and Martino, Silvana and Rondelli, Roberto and Consolini, Rita and Ruga, Ezia Maria and Cardinale, Fabio and Finocchi, Andrea and Romiti, Maria Luisa and Martire, Baldassarre and Bacchetta, Rosa and Albano, Veronica and Carotti, Adriano and Specchia, Fernando and Montin, Davide and Cirillo, Emilia and Cocchi, Guido and Trizzino, Antonino and Bossi, Grazia and Milanesi, Ornella and Azzari, Chiara and Corsello, Giovanni and Pignata, Claudio and Aiuti, Alessandro and Pietrogrande, Maria Cristina and Marino, Bruno and Ugazio, Alberto Giovanni and Plebani, Alessandro and Rossi, Paolo} } @article {1922, title = {Clinical and laboratory features of 103 patients from 42 Italian families with inherited thrombocytopenia derived from the monoallelic Ala156Val mutation of GPIbα (Bolzano mutation).}, journal = {Haematologica}, volume = {97}, year = {2012}, month = {2012 Jan}, pages = {82-8}, abstract = {

BACKGROUND: Bernard-Soulier syndrome is a very rare form of inherited thrombocytopenia that derives from mutations in GPIbα, GPIbβ, or GPIX and is typically inherited as a recessive disease. However, some years ago it was shown that the monoallelic c.515C>T transition in the GPIBA gene (Bolzano mutation) was responsible for macrothrombocytopenia in a few Italian patients.

DESIGN AND METHODS: Over the past 10 years, we have searched for the Bolzano mutation in all subjects referred to our institutions because of an autosomal, dominant form of thrombocytopenia of unknown origin.

RESULTS: We identified 42 new Italian families (103 cases) with a thrombocytopenia induced by monoallelic Bolzano mutation. Analyses of the geographic origin of affected pedigrees and haplotypes indicated that this mutation originated in southern Italy. Although the clinical expression was variable, patients with this mutation typically had a mild form of Bernard-Soulier syndrome with mild thrombocytopenia and bleeding tendency. The most indicative laboratory findings were enlarged platelets and reduced GPIb/IX/V platelet expression; in vitro platelet aggregation was normal in nearly all of the cases.

CONCLUSIONS: Our study indicates that monoallelic Bolzano mutation is the most frequent cause of inherited thrombocytopenia in Italy, affecting 20\% of patients recruited at our institutions during the last 10 years. Because many people from southern Italy have emigrated during the last century, this mutation may have spread to other countries.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Bernard-Soulier Syndrome, Child, Child, Preschool, Family Health, Female, Heterozygote, Humans, Infant, Italy, Male, Membrane Glycoproteins, Middle Aged, Mutation, Missense, Platelet Aggregation, Platelet Count, Platelet Glycoprotein GPIb-IX Complex, Polymorphism, Genetic, Thrombocytopenia, Thrombopoietin, Tubulin, Young Adult}, issn = {1592-8721}, doi = {10.3324/haematol.2011.050682}, author = {Noris, Patrizia and Perrotta, Silverio and Bottega, Roberta and Pecci, Alessandro and Melazzini, Federica and Civaschi, Elisa and Russo, Sabina and Magrin, Silvana and Loffredo, Giuseppe and Di Salvo, Veronica and Russo, Giovanna and Casale, Maddalena and De Rocco, Daniela and Grignani, Claudio and Cattaneo, Marco and Baronci, Carlo and Dragani, Alfredo and Albano, Veronica and Jankovic, Momcilo and Scianguetta, Saverio and Savoia, Anna and Balduini, Carlo L} }