Short communication
Ataxia with vitamin E deficiency (AVED); an example of the contribution of research in molecular genetic to counselling in Morocco
L’ataxie par hypovitaminose E ; un exemple de recherche mole´culaire dans le conseil ge´ne´tique
H. Bellayou
a, H. Dehbi
a, M. Bourezgui
b, I. Slassi
b, S. Nadifi
a,*
aLaboratoire de génétique médicale, faculté de médecine et de pharmacie, CHU Ibn-Rochd, 19, rue Ibn-Ziad, BP 9154, 10000 Casablanca, Morocco
bService de neurologie, CHU Ibn-Rochd, 10000 Casablanca, Morocco Received 3 June 2008;accepted 30 September 2008
Available online 26 November 2008
Keywords:Ataxia; Vitamin E deficiency; Autosomal recessive disease; Molecular research; 744delA mutation; Genea-tocopherol(a-TTP); Genetic counselling;
Morocco
Dear Sir,
The ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease, more frequent in North Africa than in Europe, characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich ataxia (FA); with dysarthria, hyporeflexia and reduced vibration sense. Sometimes, it is associated with cardiomyopathy and retinitis pigmentosa
[1]. It is caused by thealteration of gastro-intestinal absorption of vitamin E, but no other lipids
[2].Vitamin E supplementation improves symptoms and prevents disease progress
[3].The mutations are located at the gene
a-tocopherol(a-TTP) at the chromosome 8q13
[4].The reported prevalence in European, North American, Asiatic and North Africa is quite variable depending on their ethnic origins. However, various investigators have shown a high prevalence of the mutation 513insTT in Europe and North America
[5]; the most common mutation found in Japan is amissense change, H101Q, associated with a very mild phenotype and late onset
[6]. In North Africa (Tunisia,Morocco, Algeria)
[5,7,8], the 744delA mutation is the mostwidespread, with a founder effect.
In this study, we show the positive impact of genetic counselling and the contribution of research 744delA mutation of the (a-TTP) gene among families who had a first child with AVED.
The 744delA mutation was detected by
MboIIrestriction digestion of a PCR fragment containing part of exon 3 of the
a- TTPgene
[4]. The 744delA abolish the site ofMboIIrestriction.
The restriction fragments were electrophoresed on 3% agarose gel stained with ethidium bromide and visualized under ultraviolet light (Fig. 1).
The last two years for which we made available to neurologists molecular analysis of the 744delA for AVED patients; also for risk members of the family during genetic counselling. In families who had a child with ataxia, we conducted a systematic screening of the 744delA mutation of the
a-TTPgene.
We could discover five new cases carrying the deletion in homozygous state even before the onset of disease: two brothers, a sister and two cousins from a consanguineous marriage.
These cases have received preventative treatment by supplementation of vitamin E, this early treatment would prevent or report the symptoms of ataxia.
Morocco is a country with a strong tendency to consangui- neous marriage which unfortunately led to a very high rate of autosomal recessive diseases.
AVED is a very good example of a disease in which genetic counselling really plays its role to prevent outbreak of the
Pathologie Biologie 57 (2009) 425–426
* Corresponding author.
E-mail addresses:labgenmed@yahoo.fr,nadifi@fmpc.ac.ma(S. Nadifi).
0369-8114/$–see front matter#2008 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.patbio.2008.09.014
disease, not only in the offspring but also at all related. First, molecular analysis is very simple because it is a predominant mutation in our context the Maghreb 744delA and technically easy to research. Also, there is a treatment that is the supply of vitamin E, which allows a reduction in symptoms already
installed in patients and prevention for those who do not yet have the disease. This is unfortunately not possible for any diseases, the research the mutation at the related of the index case is an ethical problem in late-onset diseases, when there is no means to prevent or delay the signs of the disease. In these cases, genetic counselling can calculate the risk of having another case in the family and proposes a prenatal diagnosis to the parents who want to have other children.
References
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[8] Benomar A, Yahyaoui M, Meggouh F, Bouhouche A, Boutchich M, Bouslam N, et al. Clinical comparison between AVED patients with 744delA mutation and Friedreich ataxia with GAA expansion in 15 Moroccan families. J Neurol Sci 2002;198:25–9.
Fig. 1. The 744delA mutation was detected byMboIIrestriction digestion.M:
Ladder,ND: PCR control (fragment 94 pb),N: Normal individual had two fragments (54 and 40 pb). 744delA-/- Homozygous patient for 744delA (frag- ment 94 pb).
H. Bellayou et al. / Pathologie Biologie 57 (2009) 425–426 426
