Deletions of NF1 gene and exons detected by multiplex ligation-dependent probe amplification.

To estimate the contribution of single and multi-exon NF1 gene copy-number changes to the NF1 mutation spectrum, we analysed a series of 201 Italian patients with neurofibromatosis type 1 (NF1). Of these, 138 had previously been found, using denaturing high-performance liquid chromatography or protein truncation test, to be heterozygous for intragenic NF1 point mutations/deletions/insertions, and were excluded from this analysis. The remaining 63 patients were analysed using multiplex ligation-dependent probe amplification (MLPA), which allows detection of deletions or duplications encompassing >or=1 NF1 exons, as well as entire gene deletions. MLPA results were validated using real-time quantitative PCR (qPCR) or fluorescent in situ hybridisation. MLPA screening followed by real-time qPCR detected a total of 23 deletions. Of these deletions, six were single exon, eight were multi-exon, and nine were of the entire NF1 gene. In our series, deletions encompassing >or=1 NF1 exons accounted for approximately 7% (14/201) of the NF1 gene mutation spectrum, suggesting that screening for these should now be systematically included in genetic testing of patients with NF1.

Leopard syndrome.

The L.E.O.P.A.R.D. syndrome is an autosomal, dominant disorder with characteristic features that include: multiple lentigines, café au lait spots, electrocardiographic conduction abnormalities, ocular hypertelorism, obstructive cardiomyopathy, pulmonary stenosis, abnormal (male) genitalia, retardation of growth, and deafness. Patients do not usually present all the clinical features traditionally associated with the disorder. Indeed, several features are not present until late in life and do not become clinically manifest until puberty. It has been observed that this syndrome is caused by a "missense" mutation in PTPN11, a gene encoding the protein tyrosine phosphatase SHP-2 located on chromosome 12q22. A diagnosis of LEOPARD syndrome may be established exclusively on the basis of clinical criteria. In our case, the patient was diagnosed with the syndrome late in his life when he was already exhibiting all its distinctive clinical features. We have reported the case of a LEOPARD syndrome patient exhibiting extremely elongated vertebral and basilar arteries previously undescribed in the literature.

Pheochromocytoma associated with adrenocortical tumor in the same gland. Two case reports and literature review.

Pheochromocytomas are catecholamine-producing neuroendocrine tumours arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglionic system that show 2 distinctive features, rarity and clinical variability. Pheochromocytoma occasionally is associated with pathological lesions of the adrenal cortex. We present 2 cases of patients referred to our hospital with a finding of clinical suspected pheochromocytoma. Both of them were hypertensive; the first patient with typical symptoms of pheochromocytoma and the second patient with chest pain and hypertension resistant to pharmacological treatment. The diagnosis of pheochromocytoma was confirmed in both cases with laboratory analysis and the lesion was achieved by employing 3 imaging techniques: computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphy with (123)I-metaiodobenzilguanidine (MIBG). The patients underwent adrenalectomy and in the same adrenal gland we found a pheochromocytoma associated with a nonfunctioning cortical adenoma. As far as we know few cases with this association are available in the literature.