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Communication Dans Un Congrès Année : 2011

A multiplex kindred with severe Buruli Ulcer dis playing Mendelian inheritance

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Buruli Ulcer (BU), caused by Mycobacterium ulcerans, is the third most common mycobacteriosis worldwide after tuberculosis and leprosy, and has been flagged in 1998 by the World Health Organization as an emerging neglected infectious disease.  The physiopathology of Mycobacterium ulcerans infection primarily involves the lipidic toxin mycolactone, a unique feature among
mycobacteria. The resulting extensive skin ulcers and/or osteomyelitis cause pathologic scarring responsible for severe life-lasting functional disabilities in the affected population, mainly composed of children of less than 15 year of age.  Buruli ulcer mainly strikes in Western Sub-Saharan Africa but cases have been reported in more than 30 countries worldwide. A common characteristic of the endemic countries consists in the extreme clustering of BU cases in families living in the vicinity of slow-flowing or stagnant waters in rural areas.  However, only a fraction of these heavily exposed individuals develop Buruli ulcer, which leads us to hypothesize a genetic etiology accounting for this variability.   
To tackle this issue, we adopted an extreme-phenotype strategy, which consisted in recruiting the most severe of  the  >1,500 BU cases diagnosed and treated during the last 7 years at the Centre de Détection et de Traitement de l'Ulcère de Buruli in Pobè, Benin. We report here the analysis of a single highly-informative consanguineous family in which two siblings were affected with exceptionally severe PCR-confirmed BU. The index case suffered from a multifocal edematous form of BU, which disseminated under treatment and involved the four limbs, eventually requiring amputation to heal. Her sister suffered from an edematous form which affected the right arm from shoulder to fingers.  Blood was obtained from the 2 parents, 2 affected and 3 unaffected children. DNA was processed for the genotyping of >900,000 Single Nucleotide Polymorphisms by the Affymetrix Genome-Wide 6.0 array.  After quality control procedures, 120,156 independent SNPs were used for linkage analysis by homozygosity mapping. Three regions, on chromosome 5 and 8, cosegregated with the affected status following a Mendelian recessive inheritance mode, i.e. were shared homozygous by descent by the 2 affected individuals but not the 3 unaffected siblings (yielding the maximum possible LOD score given the pedigree. Sequencing of genes in these regions is currently ongoing and show promising results.  This first description of a genetic etiology for extremely severe BU will have far reaching biological and medical implications.  

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Dates et versions

hal-03137508 , version 1 (10-02-2021)


  • HAL Id : hal-03137508 , version 1
  • OKINA : ua11324


Quentin Vincent, Annick Chauty, Marie-Françoise Ardant, Hugues Dokponou, Jacques Gnossike, et al.. A multiplex kindred with severe Buruli Ulcer dis playing Mendelian inheritance. 14th annual meeting on Buruli ulcer, 2011, Genève, Suisse. pp.112. ⟨hal-03137508⟩
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