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

Statins in the treatment of acute ischemic stroke

3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (also known as statins) are drugs active in the blockade of cholesterol synthesis and thus lowering cholesterol serum levels. Since their discovery, experimental evidence showed that statins strongly reduced atherogenesis and the risk of acute ischemic complications, such as acute myocardial infarction and stroke. More recently, direct anti-atherosclerotic effects of statins (independently of lipid profile improvement) have been also shown, suggesting new potential applications for these drugs in both primary and secondary prevention of acute cardiovascular events. Despite some controversies exist, the use of statins has been shown to improve both incidence and survival in acute ischemic stroke. The molecular mechanisms underlying statin-mediated clinical benefits were recently identified in the reduction of carotid plaque vulnerability and the increase of neuroprotection. In the present review, we will update evidence on the promising results with statins to improve ischemic stroke outcomes

Clinical and molecular characterization of a patient with interstitial 6q21q22.1 deletion

Background: Interstitial 6q deletions, involving the 6q15q25 chromosomal region, are rare events characterized by variable phenotypes and no clear karyotype/phenotype correlation has been determined yet. Results: We present a child with a 6q21q22.1 deletion, characterized by array-CGH, associated with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, skeletal, muscle, and brain anomalies. Discussion: In our patient, the 6q21q22.1 deleted region contains ten genes (TRAF3IP2, FYN, WISP3, TUBE1, LAMA4, MARCKS, HDAC2, HS3ST5, FRK, COL10A1) and two desert gene regions. We discuss here if these genes had some role in determining the phenotype of our patient in order to establish a possible karyotype/phenotype correlation

Response to rituximab in 3 children with opsoclonus-myoclonus syndrome resistant to conventional treatments.

Background:Essential tremor (ET) is the most common movement disorder world-wide. Three susceptibility loci on chromosomes 3q13, 2p24.1, and 6p23 have beenreported, but no causative genes were found. The Ser9Gly variant of dopamine D3receptor (DRD3) receptor was found associated to ET in a French and US popula-tion.Methods:A case\u2013control study to evaluate the association between the Ser9Glyvariant and ET was performed in a cohort of 116 Italian patients with familial ET andin 158 normal controls.Results:No significant difference in allele and genotype fre-quencies was found between the two groups.Conclusions:These results do not supportan association between DRD3 Ser9Gly and susceptibility to ET in Italian patients

Identification of a rare 17p13.3 duplication including the <it>BHLHA9</it> and <it>YWHAE</it> genes in a family with developmental delay and behavioural problems

<p>Abstract</p> <p>Background</p> <p>Deletions and duplications of the <it>PAFAH1B1</it> and <it>YWHAE</it> genes in 17p13.3 are associated with different clinical phenotypes. In particular, deletion of <it>PAFAH1B1</it> causes isolated lissencephaly while deletions involving both <it>PAFAH1B1</it> and <it>YWHAE</it> cause Miller-Dieker syndrome. Isolated duplications of <it>PAFAH1B1</it> have been associated with mild developmental delay and hypotonia, while isolated duplications of <it>YWHAE</it> have been associated with autism. In particular, different dysmorphic features associated with <it>PAFAH1B1</it> or <it>YWHAE</it> duplication have suggested the need to classify the patient clinical features in two groups according to which gene is involved in the chromosomal duplication.</p> <p>Methods</p> <p>We analyze the proband and his family by classical cytogenetic and array-CGH analyses. The putative rearrangement was confirmed by fluorescence in situ hybridization.</p> <p>Results</p> <p>We have identified a family segregating a 17p13.3 duplication extending 329.5 kilobases by FISH and array-CGH involving the <it>YWHAE</it> gene, but not <it>PAFAH1B1,</it> affected by a mild dysmorphic phenotype with associated autism and mental retardation. We propose that <it>BHLHA9</it>, <it>YWHAE</it>, and <it>CRK</it> genes contribute to the phenotype of our patient. The small chromosomal duplication was inherited from his mother who was affected by a bipolar and borderline disorder and was alcohol addicted.</p> <p>Conclusions</p> <p>We report an additional familial case of small 17p13.3 chromosomal duplication including only <it>BHLHA9</it>, <it>YWHAE,</it> and <it>CRK</it> genes. Our observation and further cases with similar microduplications are expected to be diagnosed, and will help better characterise the clinical spectrum of phenotypes associated with 17p13.3 microduplications.</p