A Founder Effect of c.257+2T > C Mutation in NCF2 Gene Underlies Severe Chronic Granulomatous Disease in Eleven Patients

Khaoula Ben-Farhat; Imen Ben-Mustapha; Meriem Ben-Ali; Karen Rouault; Saber Hamami; Amel Ben-Chehida; Najla Mekki; Beya Larguèche; Zohra Fitouri; Selim Abdelmoula; Monia Khemiri; Sihem Barsaoui; Mohamed-Neji Guediche; Samir Boukthir; Jalel Chemli; Mohamed-Ridha Barbouche

doi:10.1007/s10875-016-0299-9

A Founder Effect of c.257+2T > C Mutation in NCF2 Gene Underlies Severe Chronic Granulomatous Disease in Eleven Patients

Khaoula Ben-Farhat ^{1, 2} Imen Ben-Mustapha ^{1, 2} Meriem Ben-Ali ^{1, 2} Karen Rouault ³ Saber Hamami ⁴ Amel Ben-Chehida ⁵ Najla Mekki ^{6, 1, 2} Beya Larguèche ² Zohra Fitouri ⁷ Selim Abdelmoula ⁵ Monia Khemiri ⁸ Sihem Barsaoui ⁸ Mohamed-Neji Guediche ⁴ Samir Boukthir ⁹ Jalel Chemli ¹⁰ Mohamed-Ridha Barbouche ^{1, 2, 6}

1 Tunis El Manar University

2 LR11IPT02 - Laboratoire de Transmission, Contrôle et Immunobiologie des Infections

3 Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)

4 Department of Pediatrics [Monastir]

5 Department of Pediatrics [Tunis]

6 Faculté de Médecine de Tunis

7 Department of Emergency and Consultations

8 Pediatrics Department A, Children's Hospital of Tunis

9 Department of Pediatrics C, Children's Hospital of Tunis

10 Department of Pediatrics, Sahloul Hospital, Sousse, Tunisia

Abstract : Chronic granulomatous disease (CGD) is the prototypic functional neutrophil disorder caused by genetic defects in one of the five genes encoding the superoxide-generating nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase subunits of phagocytes. Mutations causing the most prevalent form of CGD in western populations are located in the X-linked-CYBB gene. The four remaining autosomal recessive (AR) forms collectively account for one-third of CGD cases. We investigated the clinical and molecular features of eleven patients with CGD from 6 consanguineous families, originating from contiguous regions in the west of Tunisia. The patients' clinical phenotype is characterized by a high incidence of mycobacterial infections. Five out of the eleven patients died despite treatment arguing in favor of a severe clinical form of CGD. These findings correlated with the absence of functional p67phox protein as well as the absence of residual reactive oxygen intermediates (ROI) production. Genetic analysis showed the presence, in all patients, of a unique mutation (c.257 + 2T > C) in NCF2 gene predicted to affect RNA splicing. Segregating analysis using nine polymorphic markers overlapping the NCF2 gene revealed a common haplotype spanning 4.1 Mb. The founder event responsible for this mutation was estimated to have arisen approximately 175 years ago. These findings will facilitate the implementation of preventive approaches through genetic counseling in affected consanguineous families.

Keywords : NCF2 gene Chronic granulomatous disease Tunisia founder effect consanguinity

Type de document :

Article dans une revue

Journal of Clinical Immunology, Springer Verlag, 2016, 36 (6), pp.547-554. 〈10.1007/s10875-016-0299-9〉

Domaine :

Sciences du Vivant [q-bio]

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Contributeur : Institut Pasteur Tunis <>
Soumis le : jeudi 29 décembre 2016 - 10:04:23
Dernière modification le : lundi 5 février 2018 - 15:22:14

A Founder Effect of c.257+2T > C Mutation in NCF2 Gene Underlies Severe Chronic Granulomatous Disease in Eleven Patients

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