Cephalalgia, myopathy and familial dementia with CADASIL-like MRI and multiple mtDNA deletions
Poster
Data di Pubblicazione:
2008
Citazione:
Cephalalgia, myopathy and familial dementia with CADASIL-like MRI and multiple mtDNA deletions / M. Servida, L. Napoli, D. Ronchi, P. Ciscato, A. Bordoni, A. Prelle, G.P. Comi, M. Moggio, N. Bresolin, M. Sciacco. - In: JOURNAL OF NEUROLOGY. - ISSN 0340-5354. - 255:Suppl. 2(2008 Jun), pp. P596.148-P596.148. ((Intervento presentato al 18. convegno Meeting of the European Neurological Society : Symposia and Free Communications : June, 7th - 11th tenutosi a Nice nel 2008.
Abstract:
To describe a patient with cephalalgia, fatiguability,CADASIL-like
brain MRI, family history for dementia and no Notch3 mutations, whose
muscle biopsy shows signs of mitochondrial dysfunction.
Methods: A 67 years old man came to our observation with a several year
history of episodic olocranic cephalagia with nausea and vomiting associated,
in the last seven years, with easy fatiguability,myalgias and slight hyperckemia
(450–500 U/l). EMG was myopathic. A brain MRI showed multiple
confluent hyperintense lesions in the subcortical and deep white matter.
Neuropsychological examination was normal. EKG showed anterior left
hemiblock with mild heart dilatation and 40 % EF at echocardiography.
Familiar history was positive for dementia (mother and the 2 maternal
aunts). The grand-daughter of one of the two aunts (daughter of a daughter)
is affected with schizophrenia. No cognitive problems are reported in the
three maternal uncles.
The patient underwent skeletal muscle biopsy of left biceps muscle
which we studied by histological, histochemical and immunohistochemical
(dystrophin, sarcoglycans, caveolin,merosin) methods.Southern blot analysis of the mitochondrial DNA (mtDNA), search for MELAS and MERRF
mtDNA point mutations and a genetic test for Notch3 gene (CADASIL) were
also performed.
Results:Muscle biopsy only showed some fiber size variability and a few
COX-negative fibers, half of which ragged red. Southern blot analysis of
mtDNA was positive for multiple deletions, which were confirmed by PCR.
A3243G, A8344G and A8356G mtDNA point mutations were absent. No
Notch3 mutations were found.
Conclusions: recent studies have demonstrated that Notch3 gene mutations
may also manifest as neuropathy and myopathy and, particularly, cooccur
with, and,possibly,predispose to,mtDNA mutations (Finsterer, 2007).
A mitochondrial encephalopathy with CADASIL-like MRI, no Notch3 mutations
and an 8.3 Kb mtDNA macrodeletion has been described in a patient
with typical clinical features of mitochondrial disorder and negative family
history (Akhvledani et al, 2007). In our case, we found mtDNA multiple deletions,
but no Notch3 mutations in a patient with morphological evidence of
mitochondrial dysfunction, but clinical features and family history suggestive
of CADASIL. Search for nuclear DNA mutations in genes responsible for
mtDNA multiple deletions is underway.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
M. Servida, L. Napoli, D. Ronchi, P. Ciscato, A. Bordoni, A. Prelle, G.P. Comi, M. Moggio, N. Bresolin, M. Sciacco
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