Publications (18) View all
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Article: An additional family with association of hereditary thrombocytosis and transverse limb deficiency: Confirmation of a rare clinical spectrum.
American Journal of Medical Genetics Part A 11/2012; · 2.39 Impact Factor -
Article: Genetics of human enteric neuropathies.
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ABSTRACT: Knowledge of molecular mechanisms that underlie development of the enteric nervous system has greatly expanded in recent decades. Enteric neuropathies related to aberrant genetic development are thus becoming increasingly recognized. There has been no recent review of these often highly morbid disorders. This review highlights advances in knowledge of the molecular pathogenesis of these disorders from a clinical perspective. It includes diseases characterized by an infantile aganglionic Hirschsprung phenotype and those in which structural abnormalities are less pronounced. The implications for diagnosis, screening and possible reparative approaches are presented.Progress in Neurobiology 02/2012; 96(2):176-89. · 8.87 Impact Factor -
Article: Intracranial calcification in early infantile Krabbe disease: nothing new under the sun.
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ABSTRACT: We report the cases of three children, one male and two females, with a diagnosis of early infantile Krabbe disease demonstrating intracranial calcification on computed tomography (CT). The pattern of calcification was similar in all individuals and involved the internal capsule and cerebral white matter. The presence of calcification caused some diagnostic confusion in what was otherwise a typical clinical and radiological presentation. This finding is not new and has previously been described in publications from the 1980s and 1990s reporting the CT and magnetic resonance imaging appearances of Krabbe disease. With increasing use of magnetic resonance as the first imaging modality for investigation of neurological disorders, characteristic CT appearances may be forgotten. This report serves as a reminder that Krabbe disease should be included in the differential diagnosis of disorders causing intracranial calcification.Developmental Medicine & Child Neurology 12/2011; 54(4):376-9. · 2.92 Impact Factor -
Article: Two distinct thyroid tumours in a patient with Cowden syndrome carrying both a 10q23 and a mitochondrial DNA germline deletion.
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ABSTRACT: Cowden syndrome (CS) is an autosomal dominant disorder characterised by macrocephaly, specific mucocutaneous features and predisposition to benign and malignant tumours. Detectable mutations in the PTEN gene account for 80-85% of cases. Here, the authors report a patient with macrocephaly and typical CS mucocutaneous features who developed dysplastic cerebellar gangliocytoma and two synchronous thyroid cancers of papillary and oncocytic type, in whom a germline 500-Kb deletion on chromosome 10q23 including PTEN was detected. Molecular characterisation of thyroid cancer led to the identification of the oncogenic BRAFV600E mutation in the papillary carcinoma. BRAFV600E has been proposed to cause cancer only in the presence of a tumour-suppressor mutation, which, in this case, could be the PTEN deletion. In the oncocytic carcinoma, a large deletion in the mitochondrial-DNA-encoded MTND1 was found, associated with respiratory complex I disassembly, which was subsequently shown to be a constitutional, de novo genetic lesion. This is the first reported case of a patient with CS carrying constitutional deletions in both the nuclear and the mitochondrial genome that might help elucidate some aspects of CS pathogenesis.Journal of Medical Genetics 09/2011; 48(11):779-82. · 6.36 Impact Factor -
Article: FA2H-related disorders: a novel c.270+3A>T splice-site mutation leads to a complex neurodegenerative phenotype.
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ABSTRACT: Homozygous mutations in the gene for fatty acid 2-hydroxylase (FA2H) have been associated in humans with three neurodegenerative disorders: complicated spastic paraplegia (SPG35), leukodystrophy with spastic paraparesis and dystonia, and neurodegeneration with brain iron accumulation. Here, we describe a novel homozygous c.270+3A>T mutation in an Italian consanguineous family. In two affected brothers (age at molecular diagnosis 22y and 15y; age at last follow-up 24y and 17y), altered FA2H function led to a severe phenotype, with clinical features overlapping those of the three FA2H-associated disorders. Both patients showed childhood onset progressive spastic paraparesis, mild pyramidal and cerebellar upper limb signs, severe cognitive impairment, white-matter disease, and cerebellar, brainstem, and spinal cord atrophy. However, absence of dystonia, drowsiness episodes, and a subtle globus pallidus involvement suggested that FA2H mutations result in a clinical spectrum, rather than causing distinct disorders. Although clinical heterogeneity is apparent, larger numbers of patients are needed to establish more accurate genotype-phenotype correlations.Developmental Medicine & Child Neurology 05/2011; 53(10):958-61. · 2.92 Impact Factor
