Karen Rouault

Université de Bretagne Occidentale, Brest, Brittany, France

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Publications (7)33 Total impact

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    ABSTRACT: The dissection of S116 in more than 1500 individuals from Atlantic Europe and the Iberian Peninsula has provided important clues about the controversial evolutionary history of M269. First, the results do not point to an origin of M269 in the Franco-Cantabrian refuge, owing to the lack of sublineage diversity within M269, which supports the new theories proposing its origin in Eastern Europe. Second, S116 shows frequency peaks and spatial distribution that differ from those previously proposed, indicating an origin farther west, and it also shows a high frequency in the Atlantic coastline. Third, an outstanding frequency of the DF27 sublineage has been found in Iberia, with a restricted distribution pattern inside this peninsula and a frequency maximum in the area of the Franco-Cantabrian refuge. This entire panorama indicates an old arrival of M269 into Western Europe, because it has generated at least two episodes of expansion in the Franco-Cantabrian area. This study demonstrates the importance of continuing the dissection of the M269 lineage in different European populations because the discovery and study of new sublineages can adjust or even completely revise the theories about European peopling, as has been the case for the place of origin of M269.European Journal of Human Genetics advance online publication, 17 June 2015; doi:10.1038/ejhg.2015.114.
    European journal of human genetics: EJHG 06/2015; DOI:10.1038/ejhg.2015.114 · 4.35 Impact Factor

  • Journal of Cystic Fibrosis 06/2015; 14:S31. DOI:10.1016/S1569-1993(15)30097-7 · 3.48 Impact Factor
  • D. Guellec · K. Rouault · V. Scotet · F. Guillemin · C. Ferec · A. Saraux ·
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    ABSTRACT: Background Congenital dislocation of the hip (CDH), which is one of the most common skeletal congenital anomalies, results from an abnormality of the seating of the femoral head in the acetabulum. Importance of misalignment of femoral head defines different phenotypes ranging from luxation to mild forms of acetabular dysplasia (AD). CDH is a multifactorial disease with a strong genetic component attested by ethnical predispositions and familial aggregation. Recently, several studies reported the association between functional polymorphism of the 5'-untranslated region of GDF5 (Growth/Differentiation Factor 5) and CDH, a region that have also been reported to be associated with osteoarthritis. Objectives The main goal of our study was to assess whether GDF5 is associated with mild forms of AD in adult patients with hip osteoarthritis. Methods 131 Caucasian patients from the KHOALA (Knee or Hip Osteoarthritis Long Term Assessment) cohort with hip osteoarthritis were included in this study. All patients met both American College of Rheumatology and Kellgren and Lawrence (≥2) criteria for osteoarthritis. Patients underwent a morphological evaluation at both hips, based on standard anteroposterior and lateral X-rays. The morphological parameters retained here were the acetabular depth, VCE and HTE angles. Cut-off values to define AD were: VCE angle ≤20 °, HTE angle >12 °, or acetabular depth <9 mm. All patients were genotyped for two tagSNPs: rs143384 (C/T) and rs143383 (C/T), using the TaqMan® method. Association between SNPs and abnormal morphological values was tested using EpiInfo v6.04. An analysis of variance (ANOVA) was conducted to compare mean values of morphological parameters among groups defined by the genotypes. Results 45.8% (60/131) of patients had at least one morphological parameter consistent with AD. 29.8% (39/131) had abnormal HTE, 25.2% (33/131) had abnormal acetabular depth, and 17.6% (23/131) had abnormal VCE. The case-control study revealed a significant association between rs143383 variant and AD, when defined by insufficient acetabular depth. Individuals carrying CT genotype had a 5 fold higher prevalence of AD compared to those carrying CC genotype (95% CI: [0.95-35.63], p=0.030). Prevalence of AD was not significantly increased among patients carrying TT genotype (OR TT vs. CC =4.03, 95% CI: [0.72-29.33], p=0.138), whereas a significant association was observed under a dominant model (OR =4.57, 95% CI: 0.93-30.53], p=0.035). No significant association with out of range HTE and VCE values was observed. For each SNP, mean VCE, HTE, and acetabular depth values were compared among the three groups defined by their genotypes.For rs143383 variant, a significant difference in acetabular depth was observed among individuals presenting at least one morphological parameter consistent with AD (ANOVA: F =6.19, p=0.004 in the right hip and F =7.59, p=0.001 in the left hip). Conclusions This study confirms the association between GDF5 polymorphisms and CDH. It is the first publication to report an association between GDF5 and adult AD in context of hip osteoarthritis. Our results suggest an association between rs143383 and insufficient acetabular depth that should be assessed in further studies. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2371
    Annals of the Rheumatic Diseases 06/2014; 73(Suppl 2):804-805. DOI:10.1136/annrheumdis-2014-eular.2371 · 10.38 Impact Factor
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    ABSTRACT: Despite type I haemochromatosis (HC) is mainly associated with the HFE C282Y/C282Y genotype, a second genotype -C282Y/H63D- has mostly been described in other patients. Its association with HC, apart from any associated co-morbid factors, remains unclear and complex to interpret for physicians. This study assesses the weight of this genotype and the role of co-morbid factors in the occurrence of iron overload. This prospective study included the C282Y/C282Y (n = 172) and C282Y/H63D (n = 58) patients enrolled in a phlebotomy program between 2004 and 2007 in a blood centre of western Brittany (Brest, France), where HC is frequent. We compared prevalence of these two genotypes, as well as patients' profile regarding degree of iron overload and prevalence of co-morbid factors. First, we confirmed the obvious deficit of C282Y/H63D compound heterozygotes among patients cared by phlebotomies. This genotype was 3.0 times less frequent than the C282Y/C282Y genotype among those patients (18.9% vs. 56.0%) whereas it was 4.9 times more frequent in the general population (4.3% vs. 0.9%; p<0.0001). Despite a similar level of hyperferritinaemia, the C282Y/H63D patients who came to medical attention had a milder plasma iron overload, reflected by a lower transferrin saturation median (52.0% vs. 84.0%; p<0.0001). They also exhibited more frequently co-morbid factors, as heavy drinking (26.0% vs. 13.9%; p = 0.0454), overweight (66.7% vs. 39.4%; p = 0.0005) or both (21.3% vs. 2.6%; p<0.0001). Ultimately, they required a lower amount of iron removed to reach depletion (2.1 vs. 3.4 g; p<0.0001), clearly reflecting their lower tissue iron. This study confirms that H63D is a discrete genetic susceptibility factor whose expression is most visible in association with other co-factors. It highlights the importance of searching for co-morbidities in these diagnostic situations and of providing lifestyle and dietary advice.
    PLoS ONE 12/2013; 8(12):e81128. DOI:10.1371/journal.pone.0081128 · 3.23 Impact Factor
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    ABSTRACT: Inherited thrombocytopenia is a heterogeneous group of disorders characterized by a reduced number of blood platelets. Despite the identification of nearly 20 causative genes in the past decade, approximately half of all subjects with inherited thrombocytopenia still remain unexplained in terms of the underlying pathogenic mechanisms. Here we report a six-generation French pedigree with an autosomal dominant mode of inheritance and the identification of its genetic basis. Of the 55 subjects available for analysis, 26 were diagnosed with isolated macrothrombocytopenia. Genome-wide linkage analysis mapped a 10.9 Mb locus to chromosome 14 (14q22) with a LOD score of 7.6. Candidate gene analysis complemented by targeted next-generation sequencing identified a missense mutation (c.137GA; p.Arg46Gln) in the alpha-actinin 1 gene (ACTN1) that segregated with macrothrombocytopenia in this large pedigree. The missense mutation occurred within actin-binding domain of alpha-actinin 1, a functionally critical domain that crosslinks actin filaments into bundles. The evaluation of cultured mutation-harboring megakaryocytes by electron microscopy and the immunofluorescence examination of transfected COS-7 cells suggested that the mutation causes disorganization of the cellular cytoplasm. Our study concurred with a recently published whole-exome sequence analysis of six small Japanese families with congenital macrothrombocytopenia, adding ACTN1 to the growing list of thrombocytopenia genes.
    PLoS ONE 09/2013; 8(9):e74728. DOI:10.1371/journal.pone.0074728 · 3.23 Impact Factor
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    ABSTRACT: Congenital dislocation of the hip (CDH) is a multifactorial disease which involves genetic factors that are still unidentified. Recently, a functional polymorphism (rs143383) of the 5'-untranslated region of GDF5 (Growth/Differentiation Factor 5) - previously reported to be associated with osteoarthritis - has been associated with CDH in a Chinese population. The aim of our study was to determine whether GDF5, known to be involved in bone, joint and cartilage morphogenesis, is also associated with CDH in Caucasians. We genotyped three tagSNPs (rs224334, rs143384, rs143383) in 239 cases and 239 controls from western Brittany (France) where CDH is frequent, and tested the association using both single-locus and haplotype-based approaches. The most significant association was observed with rs143384. The T allele of this SNP was overrepresented in cases (65.9% vs 55.9%, P=0.002). Under a recessive model, carriers of the TT genotype had a 1.71-fold higher risk of developing CDH than carriers of the other genotypes (OR(TT vs CT+CC)=1.71, 95% CI: [1.18-2.48], P=0.005). At a nominal level, the association was also significant with rs143383 (OR(TT vs CT+CC)=1.52, 95% CI: [1.05-2.19], P=0.026). The haplotype carrying the susceptibility alleles of these SNPs was also more frequent in cases (65.9% vs 55.9%, OR=1.53, 95% CI: [1.18-1.98], P=0.002). This study reports, for the first time, the association between GDF5 polymorphisms and CDH in Caucasians, and points out another polymorphism of interest that requires further investigation. Reduction in GDF5 expression might lead to developmental deficiency of ligaments and capsule in hip joint, and therefore contribute to CDH pathogenesis.
    Osteoarthritis and Cartilage 09/2010; 18(9):1144-9. DOI:10.1016/j.joca.2010.05.018 · 4.17 Impact Factor
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    ABSTRACT: Congenital dislocation of the hip (CDH), which is one of the most common congenital skeletal disorders, corresponds to an abnormal seating of the femoral head in the acetabulum. It is commonly admitted that CDH presents a genetic component. However, little is known about the genetic factors involved. This study aimed to determine the role of two potential candidate genes on chromosome 17 in CDH: HOXB9 (involved in limb embryonic development) and COL1A1 (involved in joint laxity). We set up a case-control association study (239 cases and 239 controls) in western Brittany (France) where CDH is particularly frequent. The set of informative single nucleotide polymorphisms (SNPs) in each gene was selected using Tagger and genotyped using the SNaPshot method (n=2 and n=10, respectively). The association was tested both through single-locus and haplotype-based analyses, using SAS and Haploview softwares. In addition, we carried out the transmission disequilibrium test (TDT) with the same polymorphisms from a sample of 81 trios (i.e., 81 patients included in the case-control study and their both parents). The case-control study revealed no significant association between CDH and the tagSNPs selected in both HOXB9 and COL1A1. Moreover, the TDT did not reveal distortion in allelic and haplotype transmission of the studied markers. Our study did not support an association between HOXB9 and COL1A1 and CDH in our population. These negative findings were obtained by population- and family-based designs. Analysis of the genetic component of CDH should focus on other candidate genes.
    Osteoarthritis and Cartilage 04/2009; 17(8):1099-105. DOI:10.1016/j.joca.2008.12.012 · 4.17 Impact Factor

Publication Stats

60 Citations
33.00 Total Impact Points


  • 2013-2015
    • Université de Bretagne Occidentale
      • Faculté de Médecine et des Sciences de la Santé
      Brest, Brittany, France
  • 2010
    • Centre Hospitalier Universitaire de Brest
      Brest, Brittany, France
  • 2009
    • Etablissement Français du Sang (EFS)
      Lutetia Parisorum, Île-de-France, France