Microarray based analysis of an inherited terminal 3p26.3 deletion, containing only the CHL1 gene, from a normal father to his two affected children

<p>Abstract</p> <p>Background</p> <p>terminal deletions of the distal portion of the short arm of chromosome 3 cause a rare contiguous gene disorder characterized by growth retardation, developmental delay, mental retardation, dysmorphisms, microcephaly and ptosis. The phenotype of individuals with deletions varies from normal to severe. It was suggested that a 1,5 Mb minimal terminal deletion including the two genes <it>CRBN </it>and <it>CNTN4 </it>is sufficient to cause the syndrome.</p> <p>In addition the <it>CHL1 </it>gene, mapping at 3p26.3 distally to <it>CRBN </it>and <it>CNTN4</it>, was proposed as candidate gene for a non specific mental retardation because of its high level of expression in the brain.</p> <p>Methods and Results</p> <p>we describe two affected siblings in which array-CGH analysis disclosed an identical discontinuous terminal 3p26.3 deletion spanning less than 1 Mb. The deletion was transmitted from their normal father and included only the <it>CHL1 </it>gene. The two brothers present microcephaly, light mental retardation, learning and language difficulties but not the typical phenotype manifestations described in 3p- syndrome.</p> <p>Conclusion</p> <p>a terminal 3p26.3 deletion including only the <it>CHL1 </it>gene is a very rare finding previously reported only in one family. The phenotype of the affected individuals in the two families is very similar and the deletion has been inherited from an apparently normal parent. As already described for others recurrent syndromes with variable phenotype, these findings are challenging in genetic counselling because of an evident variable penetrance.</p

Early-onset neurodegeneration with brain iron accumulationdue to PANK2 mutation

Background: Pantothenate kinase-associated neurodegeneration (PKAN) is a neurodegenerative disorder caused by pantothenate kinase (PANK2) gene mutations. Brain magnetic resonance imaging (MRI) typically shows the "eye-of-the-tiger" sign, i.e. bilateral pallidal T2 hypointensity with a small central region of T2-hyperintensity. Aims: To describe clinical and M RI findings of a boy with early-onset neurodegeneration with brain iron accumulation due to PANK2 mutation. Methods: Clinical, neuroradiological and molecular investigations have been performed. Results: At first observation (2 years and 10 months) the boy presented only with developmental delay and toe-walking and isolated T2 hyperintensity within globi pallidi on brain MRI. One year later, small rounded areas of markedly low signal within the globi pallidi on T2(*)- weighted images appeared in association with mild dystonia. PANK2 gene homozygous mutation confirmed the diagnosis of PKAN. Conclusions: In young children, PKAN should be suspected also before clinical and neuroradiological picture is fully indicative, to avoid delayed diagnosis of a genetic disease for which therapeutical options could be potentially useful if administered in paucisymptomatic subjects

Flavonoid Intake in Relation to Colorectal Cancer Risk and Blood Bacterial DNA

Flavonoids have been inversely associated to colorectal cancer (CRC) and are plausible intermediaries for the relation among gut microbiome, intestinal permeability and CRC. We analyzed the relation of flavonoid intake with CRC and blood bacterial DNA. We conducted a case&ndash;control study in Italy involving 100 incident CRC cases and 200 controls. A valid and reproducible food&ndash;frequency questionnaire was used to assess dietary habits and to estimate six flavonoid subclass intakes. We applied qPCR and 16S rRNA gene profiling to assess blood bacterial DNA. We used multiple logistic regression to derive odds ratios (ORs) of CRC and Mann&ndash;Whitney and chi-&ndash;square tests to evaluate abundance and prevalence of operational taxonomic units (OTUs) according to flavonoid intakes. Inverse associations with CRC were found for anthocyanidins (OR for the highest versus the lowest tertile = 0.24, 95% confidence interval, CI = 0.11&ndash;0.52) and flavanones (OR = 0.18, 95% CI = 0.08&ndash;0.42). We found different abundance and prevalence according to anthocyanidin and flavanone intake for OTUs referring to Oligoflexales order, Diplorickettsiaceae family, Staphylococcus, Brevundimonas, Pelomonas and Escherischia&ndash;Shigella genera, and Flavobacterium and Legionella species. The study provides evidence to a protective effect of dietary anthocyanidins and flavanones on CRC and suggests an influence of flavonoids on blood bacterial DNA, possibly through intestinal permeability changes