Orphanet J Rare Dis
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Orphanet J Rare Dis · Jan 2014
The profile and contribution of rare germline copy number variants to cancer risk in Li-Fraumeni patients negative for TP53 mutations.
The Li-Fraumeni syndrome (LFS) is an inherited rare cancer predisposition syndrome characterized by a variety of early-onset tumors. Although germline mutations in the tumor suppressor gene TP53 account for over 50% of the families matching LFS criteria, the lack of TP53 mutation in a significant proportion of LFS families, suggests that other types of inherited alterations must contribute to their cancer susceptibility. Recently, increases in copy number variation (CNV) have been reported in LFS individuals, and are also postulated to contribute to LFS phenotypic variability. ⋯ These results, in conjunction with our previous analyses, suggest that both TP53-negative and positive LFS/LFL patients present a broad spectrum of germline genetic alterations affecting multiple loci, and that the genetic basis of LFS/LFL predisposition or penetrance in many cases might reside in germline transmission of CNVs.
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Orphanet J Rare Dis · Jan 2014
Sudden unexpected fatal encephalopathy in adults with OTC gene mutations-Clues for early diagnosis and timely treatment.
X-linked Ornithine Transcarbamylase deficiency (OTCD) is often unrecognized in adults, as clinical manifestations are non-specific, often episodic and unmasked by precipitants, and laboratory findings can be normal outside the acute phase. It may thus be associated with significant mortality if not promptly recognized and treated. The aim of this study was to provide clues for recognition of OTCD in adults and analyze the environmental factors that, interacting with OTC gene mutations, might have triggered acute clinical manifestations. ⋯ This report raises awareness of the ED medical staff in considering OTCD in the differential diagnosis of sudden neurological and behavioural disorders associated with hyperammonemia at any age and in both genders. It also widens the knowledge about combined effect of genetic and environmental factors in determining the phenotypic expression of OTCD.
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Orphanet J Rare Dis · Jan 2014
Clinical and genetical heterogeneity of late-onset multiple acyl-coenzyme A dehydrogenase deficiency.
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder caused by deficiency of electron transfer flavoprotein or electron transfer flavoprotein dehydrogenase. The clinical picture of late-onset forms is highly variable with symptoms ranging from acute metabolic decompensations to chronic, mainly muscular problems or even asymptomatic cases. ⋯ Late-onset MADD is probably an underdiagnosed disease and should be considered in all patients with acute or chronic muscular symptoms or acute metabolic decompensation with hypoglycemia, acidosis, encephalopathy and hepatopathy. This may not only prevent patients from invasive diagnostic procedures such as muscle biopsies, but also help to avoid fatal metabolic decompensations.
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Orphanet J Rare Dis · Nov 2013
Abnormal centrosome and spindle morphology in a patient with autosomal recessive primary microcephaly type 2 due to compound heterozygous WDR62 gene mutation.
Autosomal recessive primary microcephaly (MCPH) is a rare neurodevelopmental disease with severe microcephaly at birth due to a pronounced reduction in brain volume and intellectual disability. Biallelic mutations in the WD repeat-containing protein 62 gene WDR62 are the genetic cause of MCPH2. However, the exact underlying pathomechanism of MCPH2 remains to be clarified. ⋯ We propose that a disruption of centrosome integrity and/or spindle organization may play an important role in the development of microcephaly in MCPH2.