Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome.

N. Agrebi; I. Ben-Mustapha; N. Matoussi; N. Dhouib; M Ben-Ali; N. Mekki; B Larguèche; M Ben-Ahmed; S. Ben Becher; M Béjaoui; Mohamed-Ridha Barbouche

doi:10.1016/j.clim.2017.06.009

Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome.

N. Agrebi ^{1, 2} I. Ben-Mustapha ^{1, 2} N. Matoussi ² N. Dhouib ² M Ben-Ali ¹ N. Mekki ¹ B Larguèche ¹ M Ben-Ahmed ¹ S. Ben Becher ² M Béjaoui ^{2, 3} Mohamed-Ridha Barbouche ^{1, 2}

1 LR11IPT02 - Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection

2 Faculté de Médecine de Tunis

3 Service d'immunohémathologie pédiatrique

Abstract : Autoimmune lymphoproliferative syndrome (ALPS) is a prototypic disorder of impaired apoptosis characterized by autoimmune features and lymphoproliferation. Heterozygous germline or somatic FAS mutations associated with preserved protein expression have been described. Very rare cases of homozygous germline FAS mutations causing severe autosomal recessive form of ALPS with a complete defect of Fas expression have been reported. We report two unrelated patients from highly inbred North African population showing a severe ALPS phenotype and an undetectable Fas surface expression. Two novel homozygous mutations have been identified underlying rare splicing defects mechanisms. The first mutation breaks a branch point sequence and the second alters a regulatory exonic splicing site. These splicing defects induce the skipping of exon 6 encoding the transmembrane domain of CD95. Our findings highlight the requirement of tight regulation of FAS exon 6 splicing for balanced alternative splicing and illustrate the importance of such studies in highly consanguineous populations.

Keywords : Splicing Consanguinity FAS Alps Autosomal recessive

Type de document :

Article dans une revue

Clinical Immunology, Elsevier, 2017, 183, pp.17-23. 〈10.1016/j.clim.2017.06.009〉

Domaine :

Sciences du Vivant [q-bio]

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https://hal-riip.archives-ouvertes.fr/pasteur-01553307
Contributeur : Anne Lassailly-Bondaz <>
Soumis le : lundi 3 juillet 2017 - 15:08:35
Dernière modification le : lundi 8 octobre 2018 - 17:44:08

Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome.

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Rare splicing defects of FAS underly severe recessive autoimmune lymphoproliferative syndrome.

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