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Levi Z.,Rabin Medical Center | Levi Z.,Tel Aviv University | Kariv R.,Tel Aviv University | Kariv R.,Tel Aviv Sourasky Medical Center | And 15 more authors.
Clinical Genetics | Year: 2015

Data on the clinical presentation of constitutional mismatch repair deficiency syndrome (CMMRD) is accumulating. However, as the extraintestinal manifestations are often fatal and occur at early age, data on the systematic evaluation of the gastrointestinal tract is scarce. Here we describe 11 subjects with verified biallelic carriage and who underwent colonoscopy, upper endoscopy and small bowel evaluation. Five subjects were symptomatic and in six subjects the findings were screen detected. Two subjects had colorectal cancer and few adenomatous polyps (19, 20years), three subjects had polyposis-like phenotype (13, 14, 16years), four subjects had few adenomatous polyps (8, 12-14years) and two subjects had no polyps (both at age 6). Of the three subjects in the polyposis-like group, two subjects had already developed high-grade dysplasia or cancer and one subject had atypical juvenile polyps suggesting juvenile polyposis. Three out of the five subjects that underwent repeated exams had significant findings during short interval. The gastrointestinal manifestations of CMMRD are highly dependent upon age of examination and highly variable. The polyps may also resemble juvenile polyposis. Intensive surveillance according to current guidelines is mandatory. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

Goldberg Y.,Hebrew University of Jerusalem | Barnes-Kedar I.,The Raphael Recanati Genetics Institute | Lerer I.,Hebrew University of Jerusalem | Halpern N.,Hebrew University of Jerusalem | And 10 more authors.
Clinical Genetics | Year: 2015

Diagnosis of Lynch syndrome (LS) may be complex. Knowledge of mutation spectrum and founder mutations in specific populations facilitates the diagnostic process. Aim of the study is to describe genetic features of LS in the Israeli population and report novel and founder mutations. Patients were studied at high-risk clinics. Diagnostics followed a multi-step process, including tumor testing, gene analysis and testing for founder mutations. LS was defined by positive mutation testing. We diagnosed LS in 242 subjects from 113 families coming from different ethnicities. We identified 54 different mutations; 13 of them are novel. Sixty-seven (59%) families had mutations in MSH2, 20 (18%) in MSH6, 19 (17%) in MLH1 and 7 (6%) in PMS2; 27% of the MSH2 mutations were large deletions. Seven founder mutations were detected in 61/113 (54%) families. Constitutional mismatch repair deficiency (CMMR-D) was identified in five families. Gene distribution in the Israeli population is unique, with relatively high incidence of mutations in MSH2 and MSH6. The mutation spectrum is wide; however, 54% of cases are caused by one of seven founder mutations. CMMR-D occurs in the context of founder mutations and consanguinity. These features should guide the diagnostic process, risk estimation, and genetic counseling. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

Pimienta A.L.,Technion - Israel Institute of Technology | Rimoin D.L.,Cedars Sinai Medical Center | Pariani M.,Cedars Sinai Medical Center | Schievink W.I.,Cedars Sinai Medical Center | Reinstein E.,The Raphael Recanati Genetics Institute
Journal of Neurology | Year: 2014

The presence of cardiovascular abnormalities in patients with spontaneous cerebrospinal fluid (CSF) leaks are not well-documented in the literature, as cardiovascular evaluation is not generally pursued if a patient does not exhibit additional clinical features suggesting an inherited connective tissue disorder. We aimed to assess this association, enrolling a consecutive group of 50 patients referred for spinal CSF leak consultation. Through echocardiographic evaluation and detailed medical history, we estimate that up to 20% of patients presenting with a spontaneous CSF leak may have some type of cardiovascular abnormality. Further, the increase in prevalence of aortic dilatation in our cohort was statistically significant in comparison to the estimated population prevalence. This supports a clinical basis for echocardiographic screening of these individuals for cardiovascular manifestations that may have otherwise gone unnoticed or evolved into a more severe manifestation. © Springer-Verlag Berlin Heidelberg 2014. Source

Baris H.N.,The Genetics Institute | Baris H.N.,Technion - Israel Institute of Technology | Weisz Hubshman M.,The Raphael Recanati Genetics Institute | Weisz Hubshman M.,Tel Aviv University | And 5 more authors.
Blood Cells, Molecules, and Diseases | Year: 2015

Bone crises in type 1 Gaucher disease are reported in long bones and occasionally in weight bearing bones and other bones, but rarely in small bones of the hands and feet. We retrospectively examined the incidence of bone pain in patients followed at the Rabin Medical Center, Israel, before and following the initiation of enzyme replacement therapy (ERT) and evaluated them for bone crises. Of 100 type I Gaucher disease patients, 30 (30%) experienced one or more bone crises. Small bone crises represented 31.5% of all bone crises and were always preceded by crises in other bones. While the incidence of long bone crises reduced after the initiation of ERT, small bone crises increased. Almost 60% of patients with bone crises were of the N370S/84GG genotype suggesting a greater susceptibility of N370S/84GG patients to severe bone complications. These patients also underwent the greatest number of splenectomies (70.6% of splenectomised patients). Splenectomised patients showed a trend towards increased long and small bone crises after surgery. Active investigation of acute pain in the hands and feet in patients in our cohort has revealed a high incidence of small bone crises. Physicians should consider imaging studies to investigate unexplained pain in these areas. © 2015 Elsevier Inc. Source

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