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Holoprosencephaly (HPE) is the most common congenital cerebral malformation in humans, characterized by impaired forebrain cleavage and midline facial anomalies. It presents a high heterogeneity, both in clinics and genetics. We have developed a novel targeted next-generation sequencing (NGS) assay and screened a cohort of 257 HPE patients. Mutations with high confidence in their deleterious effect were identified in approximately 24% of the cases and were held for diagnosis, whereas variants of uncertain significance were identified in 10% of cases. This study provides a new classification of genes that are involved in HPE. SHH, ZIC2, and SIX3 remain the top genes in term of frequency with GLI2, and are followed by FGF8 and FGFR1. The three minor HPE genes identified by our study are DLL1, DISP1, and SUFU. Here, we demonstrate that fibroblast growth factor signaling must now be considered a major pathway involved in HPE. Interestingly, several cases of double mutations were found and argue for a polygenic inheritance of HPE. Altogether, it supports that the implementation of NGS in HPE diagnosis is required to improve genetic counseling.

Nous rapportons notre experience de l’analyse du genotypage non invasif du RHD, RHCE et KEL1 fœtal sur sang maternel, effectuee en routine hospitaliere dans l’Unite Fonctionnelle de Biologie Materno-Fœtale du Service de Biochimie et Biologie Moleculaire de l’Hopital Nord a Marseille durant la periode 2010–2014. Pour le genotypage RHD, 19 209 femmes enceintes rhesus D negatif (RH-1) de la region PACA–Corse–Monaco ont ete analysees dans le cadre d’un depistage systematique du risque de l’alloimmunisation fœtomaternelle, ainsi que 56 patientes enceintes allo-immunisees pour l’antigene RHCE ou KEL1. Le terme de la grossesse auquel a ete realisee l’analyse etait compris entre la 5e et la 35e semaine d’amenorrhee (SA). Pour le genotypage RHD, seuls les resultats RHD negatif (RH-1) rendus avant la 13e SA ont ete controles par un deuxieme prelevement. La sensibilite, la specificite, les valeurs predictives positive et negative ainsi que l’exactitude ont ete calculees. Ces resultats nous permettent de conclure qu’il n’est pas necessaire de controler les fœtus rhesus D negatif quel que soit le terme de la grossesse. Par ailleurs, la presence de polymorphisme RHD maternel a ete detectee chez 3 % des femmes enceintes analysees. Le genotypage RHD fœtal n’a pas pu etre determine dans 1 % des cas, lorsque les patientes presentaient un polymorphisme RHD de type D-faible/D-partiel.

Unit costs used in the cost analysis. (PDF 273â kb)

Economic results using all direct medical costs collected during the trial. This supplementary material shows the economic analysis of the ICER, the cost-effectiveness plane and the acceptability curve that have been recalculated using all direct health costs (those pertaining to RHD status: biological tests, injections and visits, plus all hospital stays during the follow-up period). (PDF 358â kb)

Resume Introduction Les colobomes oculaires congenitaux sont dus a un defaut de fermeture de la fissure fœtale. Cette etude prospective (2007 a 2011) analyse les anomalies cerebrales a l’imagerie par resonance magnetique (IRM) dans une population colobomateuse. Patients et methodes Trente-cinq enfants (54 yeux) sont inclus ; 15 garcons et 20 filles, d’âge median a la premiere consultation 24,0 mois (1,0–96,0). L’IRM est pratiquee dans les deux ou trois mois suivants un examen ophtalmologique complet. Resultats Le colobome a ete bilateral dans 19 cas et unilateral dans 16. Onze types differents de colobome ont ete distingues. Sur 54 yeux, 74 % presentent un colobome papillaire dont 28 severes. Sur 35 IRM realisees, 86 % presentent des anomalies : anomalies de giration ( n = 21), dilatations des ventricules lateraux (VL) ( n = 17), dilatations des espaces de Virchow-Robin (VR) et sous arachnoidiens (ESA) ( n = 14), anomalies de signal et malformatives du tronc cerebral (TC) ( n = 14), anomalies de signal de la substance blanche (SB) ( n = 11), anomalies du corps calleux (CC) ( n = 10). Ces anomalies sont le plus souvent associees entre elles. On remarque que les anomalies de giration sont les plus frequentes. Il n’est pas retrouve de lien significatif ni entre la severite du colobome et les anomalies retrouvees ( p = 1,0) ni entre les anomalies de giration et la severite de l’atteinte du colobome ( p = 1,0). Discussion et conclusion Cette etude met en evidence, pour la premiere fois, l’existence d’anomalies cerebrales tres frequentes a l’IRM chez les enfants atteints de colobome oculaire. Ces anomalies sont a 60 % des anomalies de giration le plus souvent associees aux autres anomalies decrites.

International audience; Holoprosencephaly (HPE) is the most common congenital cerebral malformation in humans, characterized by impaired forebrain cleavage and midline facial anomalies. It presents a high heterogeneity, both in clinics and genetics. We have developed a novel targeted next-generation sequencing (NGS) assay and screened a cohort of 257 HPE patients. Mutations with high confidence in their deleterious effect were identified in approximately 24% of the cases and were held for diagnosis, whereas variants of uncertain significance were identified in 10% of cases. This study provides a new classification of genes that are involved in HPE. SHH, ZIC2, and SIX3 remain the top genes in term of frequency with GLI2, and are followed by FGF8 and FGFR1. The three minor HPE genes identified by our study are DLL1, DISP1, and SUFU. Here, we demonstrate that fibroblast growth factor signaling must now be considered a major pathway involved in HPE. Interestingly, several cases of double mutations were found and argue for a polygenic inheritance of HPE. Altogether, it supports that the implementation of NGS in HPE diagnosis is required to improve genetic counseling.

Background: Most studies of the molecular basis of Rhesus D-negative phenotype have been conducted in Caucasian and African populations. A comprehensive survey of RHD alleles was lacking in people from North Africa (Tunisians, Moroccans and Algerians) which could be very efficient for managing donors and patients carrying an RHD molecular variant. We analyse the molecular background of D-negative population in Tunisia in the present study. Materials and methods: Blood samples were collected from native Tunisians. A total of 448 D-negative donors from different regions of Tunisia were analysed by RHD genotyping according to an adopted strategy using real-time PCR, ASP-PCR and sequencing. Results: Among the 448 D-negative samples, 443 were phenotyped unequivocally as true D-negative including three molecular backgrounds which were RHD gene deletion (n = 437), RHDψ pseudogene (n = 2) and RHD-CE-D hybrid gene (n = 4) with the respective frequencies of 0*9900, 0*0023 and 0*0046. The remaining five samples, in discordance with the serological results, were identified as two weak D type 11, one weak D type 29, one weak D type 4*0 and one DBT-1 partial D. Conclusion: This study showed that the Tunisian population gets closer to Caucasians, given that the RHD gene deletion is the most prevalent cause of D-negative phenotype, but it is slightly different by the presence of the RHDψ pseudogene which was found with a very low frequency compared with that described in the African population. Nevertheless, the relative occurrence of weak D variants among studied serologically D-negative samples make necessary the adaptation of RHD genotyping strategy to the spectrum of prevalent alleles.

Objective: To compare total and fetal DNA levels in the maternal plasma in three groups: pregnancies with intrauterine growth restriction (IUGR) due to placental insufficiency (PI) and other causes, and in control pregnancies. Methods: Total as well as fetal DNA was quantified in 78 maternal plasma samples. In 19 pregnancies, the fetus presented IUGR due to PI (group A), and in 31 pregnancies due to other causes (group B). The control group comprised 28 patients (group C). DNA quantification was done using real-time quantitative PCR with a standardized pool of plasmid calibrators. DNA concentrations of the three groups were compared using non-parametric tests (Kruskal-Wallis or Mann-Whitney tests). Results: The three groups did not statistically differ regarding maternal age (mean ± SD: 30.5 ± 5.4 years), gestational age (30 ± 5.3 weeks) or the proportion of male fetuses (48.2%). Plasma total DNA was significantly higher in group A compared to groups B and C (p = 0.001 for both). An increase in fetal DNA was only observed in group A for patients beyond 28 weeks of gestation. Conclusions: The plasma total DNA level is higher in patients with IUGR due to PI. These results suggest the presence of maternal endothelial damage independently of preeclampsia.

International audience; Predicting pregnancy complications is a major topic for clinicians and biologists for maternal and fetal monitoring. Noninvasive biomarkers in maternal blood such as circulating microRNAs (miRNAs) are promising molecules to predict pregnancy disorders. miRNAs are noncoding short RNAs that regulate mRNA expression by repressing the translation or cleaving the transcript. miRNAs are released to the extracellular systemic circulation via exosomes. The discovery of plasma-or serum-derived miRNAs and of free-circulating exosomes that contain miRNAs provides useful information about the physiological or pathophysiological roles of the miRNAs. Specific placental miRNAs are present in maternal plasma in different ways depending on whether the pregnancy is normal or pathological or if there is no pregnancy. This paper focuses on placental miRNAs and extracellular miRNAs to the placenta whose misregulation could lead to pregnancy complications.

Predicting pregnancy complications is a major topic for clinicians and biologists for maternal and fetal monitoring. Noninvasive biomarkers in maternal blood such as circulating microRNAs (miRNAs) are promising molecules to predict pregnancy disorders. miRNAs are noncoding short RNAs that regulate mRNA expression by repressing the translation or cleaving the transcript. miRNAs are released to the extracellular systemic circulation via exosomes. The discovery of plasma- or serum-derived miRNAs and of free-circulating exosomes that contain miRNAs provides useful information about the physiological or pathophysiological roles of the miRNAs. Specific placental miRNAs are present in maternal plasma in different ways depending on whether the pregnancy is normal or pathological or if there is no pregnancy. This paper focuses on placental miRNAs and extracellular miRNAs to the placenta whose misregulation could lead to pregnancy complications.

The major histocompatibility complex class I related chain (MIC) is a stress-inducible protein modulating the function of immune natural killer (NK) cells, a major leukocyte subset involved in proper trophoblast invasion and spiral artery remodeling. Aim of the study was to evaluate whether upregulation of soluble MIC (sMIC) may reflect immune disorders associated to vascular pregnancy diseases (VPD). sMIC was more frequently detected in the plasma of women with a diagnostic of VPD (32%) than in normal term-matched pregnancies (1.6%,P<0.0001), with highest prevalence in intrauterine fetal death (IUDF, 44%) and vascular intrauterine growth restriction (IUGR, 39%). sMIC levels were higher in preeclampsia (PE) than in IUFD (P<0.01) and vascular IUGR (P<0.05). sMIC detection was associated with bilateral early diastolic uterine notches (P=0.037), thrombocytopenia (P=0.03), and high proteinuria (P=0.03) in PE and with the vascular etiology of IUGR (P=0.0038). Incubation of sMIC-positive PE plasma resulted in downregulation of NKG2D expression and NK cell-mediated IFN-γproduction in vitro. Our work thus suggests that detection of sMIC molecule in maternal plasma may constitute a hallmark of altered maternal immune functions that contributes to vascular disorders that complicate pregnancy, notably by impairing NK-cell mediated production of IFN-γ, an essential cytokine favoring vascular modeling.

Microdeletion of 22q11 is responsible for DiGeorge syndrome, velocardiofacial syndrome, congenital conotruncal heart defects, and related disorders. Familial transmission accounts for about 10–20 per cent of cases and most of the parents with deletions are nearly asymptomatic. This phenotypic variability makes it difficult to give appropriate genetic counselling. We report our experience on prenatal diagnosis of 22q11 deletion. We proposed prenatal detection of 22q11 microdeletion in 33 pregnancies. In two instances the parents refused prenatal diagnosis and one pregnancy ended spontaneously before the time of sampling. Fluorescent in situ hybridization (FISH) analysis on cultured amniotic cells with probes mapping in the commonly deleted region was used in the remaining 30 cases. Indications were classified into two groups. The first group included four couples with an abnormal family history of a deleted child and/or a deleted parent. No deletion was found in this group. The second one concerned pregnancies with a prenatally detected heart defect. Among these pregnancies with abnormal ultrasound findings, three deletions were found in the 26 samples tested. © 1997 John Wiley & Sons, Ltd.

A case of false-negative discrepancy between results of chorionic villi (direct preparation) and those of fetal tissue with an isochromosome 18q [i(18q)] in amniotic cells and fetal blood is reported. Fluorescence in situ hybridization (FISH) confirmed this uncommon chromosomal rearrangement. The fetus showed cyclopia and multiple congenital anomalies which have never been reported in cases of i(18q).

Resume La majorite des enfants presentant un syndrome de Di George et plus de la moitie des enfants presentant un syndrome velocardiofacial ont une microdeletion de la partie proximale du bras long du chromosome 22 (22q11). L'expression clinique de cette anomalie chromosomique est tres variable et le tableau clinique pe etre tres fruste. Observations. - Les 49 enfants âges de 0 a 15 ans porteurs d'une deletion 22q11 se presentaient cliniquement comme: syndrome de Di George typique (19 cas), syndrome velocardiofacial (14 cas), cardiopathie conotroncale avec dysmorphie (neuf cas): hypoparathyroidie (deux cas). La recherche de la microdeletion a ete effectuee par la technique d'hybridation in situ fluorescente a l'aide de sondes moleculaires specifiques de la region. Resultats. - La dysmorphie faciale apparaissait comme le seul element constant du tableau clinique. Une cardiopathie congenitale etait presente chez 84% des enfants. L'hypocalcemie etait retrouvee dans 51% des cas ( 19 37 ), l'hypo-agenesie thymique chez 83% des enfants. Neuf enfants avaient un deficit immunitaire. Les malformations associees les plus frequentes etaient les anomalies reno-urinaires; les plus severes sont les stenoses sous-glottiques. Une fente palatine a ete documentee dans 17% des cas, alors que l'insuffisance velopharyngee etait tres frequente. Deux tiers des enfants presentaient un retard psychomoteur, le plus souvent leger. Cinq enfants avaient des troubles du comportement. Parmi les 35 couples de parents testes, il a ete possible de mettre en evidence la microdeletion 22q11 chez huit meres. Conclusion. - Pour le pediatre, il est important de connaitre la variete des tableaux cliniques qui doivent amener a rechercher une deletion 22q11. Le pronostic vital est essentiellement conditionne par l'importance de la cardiopathie congenitale. A long terme, le pronostic depend de la possibilite d'un retard mental et de troubles du comportement. L'exploration familiale est indispensable. La mise en evidence de l'anomalie moleculaire chez des apparentes asymptomatiques pose de difficites problemes de conseil genetique.

Objectif : evaluer la valeur diagnostique de l’approche du genotypage rhesus fœtal a partir du plasma maternel dans une population de femmes enceintes RhD-negatif. Patientes et methodes : les prelevements plasmatiques des 65 femmes enceintes ont ete analyses. L’ADN a ete quantifie par PCR quantitative en temps reel (RQ-PCR) par multiplexage ciblant les exons 5, 7 et 10 du gene RhD, et a l’aide d’une gamme de calibration plasmidique standard. Les resultats ont ete compares avec ceux de l’analyse serologique du sang du cordon suite a l’accouchement. Resultats : le statut RhD fœtal a ete predit avec une precision de 95,38 % a partir du plasma maternel des femmes enceintes entre la 11 e et la 40 e semaine d’amenorrhee. Un faux positif, mais aucun faux negatif n’a ete identifie. La sensibilite et la specificite du test sont respectivement de 100 % et 94,44 %. Conclusion : ces resultats demontrent que l’approche de genotypage rhesus fœtal pourrait etre efficace par PCR quantitative en temps reel chez les femmes enceintes tunisiennes de phenotype RhD negatif.

Background The lethal short rib polydactyly syndromes (SRP type I-IV) are characterised by notably short ribs, short limbs, polydactyly, multiple anomalies of major organs, and autosomal recessive mode of inheritance. Among them, SRP type II (Majewski; MIM 263520) is characterised by short ovoid tibiae or tibial agenesis and is radiographically closely related to SRP type IV (Beemer-Langer; MIM 269860) which is distinguished by bowed radii and ulnae and relatively well tubulated tibiae. NEK1 mutations have been recently identified in SRP type II. Double heterozygosity for mutations in both NEK1 and DYNC2H1 in one SRP type II case supported possible digenic diallelic inheritance. Methods The aim of this study was to screen DYNC2H1 and NEK1 in 13 SRP type II cases and seven SRP type IV cases. It was not possible to screen DYNC2H1 in two patients due to insufficient amount of DNA. Results The study identified homozygous NEK1 mutations in 5/13 SRP type II and compound heterozygous DYNC2H1 mutations in 4/12 cases. Finally, NEK1 and DYNC2H1 were excluded in 3/12 SRP type II and in all SRP type IV cases. The main difference between the mutation positive SRP type II group and the mutation negative SRP type II group was the presence of holoprosencephaly and polymycrogyria in the mutation negative group. Conclusion This study confirms that NEK1 is one gene causing SRP type II but also reports mutations in DYNC2H1, expanding the phenotypic spectrum of DYNC2H1 mutations. The exclusion of NEK1 and DYNC2H1 in 3/12 SRP type II and in all SRP type IV cases further support genetic heterogeneity.

International audience; Background: Most studies of the molecular basis of Rhesus D-negative phenotype have been conducted in Caucasian and African populations. A comprehensive survey of RHD alleles was lacking in people from North Africa (Tunisians, Moroccans and Algerians) which could be very efficient for managing donors and patients carrying an RHD molecular variant. We analyse the molecular background of D-negative population in Tunisia in the present study. Materials and methods: Blood samples were collected from native Tunisians. A total of 448 D-negative donors from different regions of Tunisia were analysed by RHD genotyping according to an adopted strategy using real-time PCR, ASP-PCR and sequencing. Results: Among the 448 D-negative samples, 443 were phenotyped unequivocally as true D-negative including three molecular backgrounds which were RHD gene deletion (n = 437), RHDψ pseudogene (n = 2) and RHD-CE-D hybrid gene (n = 4) with the respective frequencies of 0*9900, 0*0023 and 0*0046. The remaining five samples, in discordance with the serological results, were identified as two weak D type 11, one weak D type 29, one weak D type 4*0 and one DBT-1 partial D. Conclusion: This study showed that the Tunisian population gets closer to Caucasians, given that the RHD gene deletion is the most prevalent cause of D-negative phenotype, but it is slightly different by the presence of the RHDψ pseudogene which was found with a very low frequency compared with that described in the African population. Nevertheless, the relative occurrence of weak D variants among studied serologically D-negative samples make necessary the adaptation of RHD genotyping strategy to the spectrum of prevalent alleles.

Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuria, pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1). Here, we review the series of 54 distinct mutations identified in 48 unrelated families. Most of them are novel and ACE mutations are the most frequent, observed in two-thirds of families (64.6%). The severity of the clinical course was similar whatever the mutated gene, which underlines the importance of a functional RAS in the maintenance of blood pressure and renal blood flow during the life of a human fetus. Renal hypoperfusion, whether genetic or secondary to a variety of diseases, precludes the normal development/ differentiation of proximal tubules. The identification of the disease on the basis of precise clinical and histological analyses and the characterization of the genetic defects allow genetic counseling and early prenatal diagnosis.

Congenital ocular colobomas are the result of a failure in closure of the embryonal fissure. We present a prospective study (2007-2011) in which we report brain MRI findings in children with ocular coloboma.Thirty-five children (54 eyes) were included; 15 boys, 20 girls with a median age of 24.0 months (1.0-96.0) at first presentation. Within 2 to 3 months following complete ophthalmologic examination, brain MRI was performed.Colobomas were bilateral in 19 cases and unilateral in 16 cases. Eleven different types of coloboma were identified. Of 54 eyes, 74% demonstrated optic nerve coloboma, of which 28 were severe. Of 35 MRI's performed, abnormalities were present in 86%: gyration abnormalities (n=21), lateral ventricular dilatation (n=17), dilatation of the Virchow-Robin and subarachnoid spaces (n=14), signal abnormalities and brain stem malformations (n=14), white matter signal abnormalities (n=11), corpus callosum abnormalities (n=10). Most of these abnormalities were related. Gyration abnormalities were the most frequent. There was no significant association between the severity of the coloboma and the abnormalities found (P=1.0). Likewise, there was no significant association of gyration abnormalities with the severity of coloboma in children (P=1.0).This study shows, for the first time, the existence of frequent cerebral abnormalities on MRI in children with ocular coloboma. The most common abnormality being gyration abnormalities, in 60% of cases.

Expression of the voltage-dependent sodium channel has been analysed in adult rat central nervous system by Northern blotting and in situ hybridization. Northern blots showed that all the territories studied express beta 2 transcripts, albeit with widely varying levels (with cerebellumhippocampusbrainbrainstemspinal cord). In situ hybridization confirmed that in these structures, all the neuronal cell bodies contain beta 2 mRNA; expression was particularly high in the granule cells of the cerebellum, in both pyramidal cell layer and dentate gyrus in the hippocampus, and in spinal cord motor neurons. Northern blots also showed that RNA extracted from optic nerve and cultured cortical astrocytes contained beta 2 mRNA, while it was totally absent from sciatic nerve. In situ hybridization evidenced the presence of a numerous population of beta 2-positive cells in cerebellum white matter, spinal cord white matter, and in corpus callosum, where frontal sections showed labelled cells arranged in the chain-like or row pattern typical of interfascicular oligodendrocytes. Combination of antiglial fibrillary acid protein (GFAP) immunofluorescent histochemistry with detection of beta 2 mRNA evidenced that expression of the transcripts was indeed restricted to GFAP-negative cells in white matter.

Most of the children with Di George syndrome and 60% of patients with velocardiofacial syndrome exhibit a microdeletion within chromosome 22q11. The phenotypic expression of this chromosomal abnormality is highly variable.Forty-nine children, 0 to 15 years of age, were demonstrated as carriers of a 22q11 microdeletion. The main referral diagnoses were: Di George syndrome (19 cases), velocardiofacial syndrome (14 cases); congenital heart defect with dysmorphism (9 cases); hypoparathyroidism (2 cases). The microdeletion was detected by fluorescent in situ hybridization with probes specific of the 22q11 region.Facial dysmorphism was the only constant feature. A congenital heart defect was present in 84% of cases. Significant hypocalcemia was documented in 51% of cases and thymic hypo or agenesis in 83%. Significant immune deficiency was documented in nine cases. The most frequent associated defects were urinary tract malformations (8 cases). A cleft palate was present in height enfants but velopharyngeal insufficiency was almost constant. Two-thirds of children had psychomotor delay, and five children exhibited behavioral problems. Of the 35 couples of parents tested, eight mothers were found to be carriers of the deletion.For the pediatrician, it is essential to know the variability of the clinical picture. The long-term prognosis is conditioned by the possibility of mental retardation and learning disabilities. Parents should be tested for the presence of the deletion. The occurrence of the microdeletion in asymptomatic relatives raises difficult problems in genetic counselling.

DiGeorge sequence (DGS) is a developmental field defect of the third and fourth pharyngeal pouches. The cardinal features of the syndrome are hypo- or aplasia of the thymus and parathyroids, congenital heart defect of the conotruncal type and characteristic facial dysmorphism. Such a pattern of malformations has been associated with various conditions but it is now well established that most cases of DGS are due to haplo-insufficiency of the chromosome 22q11 region. We report here a series of 16 patients, including a familial case. Minimal criteria for inclusion in this series were two or more of the following features: conotruncal heart defect, hypocalcaemia, hypoplastic/absent thymus and typical facial dysmorphism. Molecular analysis with specific probes of the 22q11 region was conducted in all patients according to two methods, fluorescent in situ hybridization and DNA dosage analysis. A deletion was found at the molecular level in all patients. We emphasize the fact that clinical analysis remains an important step of the diagnosis. The implication of these molecular techniques on diagnosis, prognosis and genetic counselling of DGS are discussed.

Background: Study the population presenting a polymorphism of the rhesus D in region PACA-Corse-Monaco and to correlate RHD weak polymorphism in a category of population.Study design and methods: A descriptive study, polymorphisms discovered during the fetal genotyping on maternal blood within the laboratory of biochemistry and molecular biology of the Hospital Nord in Marseille, was realized from 2008 to 2014. All in all 464 patients described according to three qualitative data: maternal geographical origins, maternal phenotype and maternal genotype. To answer the second objective, 34 patients weredescribed over the years 2013-2014.Results: In Caucasian (n=183) group was found a majority of weak/partial RHD (n=108) and C+c+E-e+ is the dominant phenotype (n=122). A majority of hybrids (n=54) was found in North Africa’s (n=131) patients and the most found phenotype is C+c+E-e+ (n=61). The prevalence of RHD pseudogene polymorphism is higher in patients from Sub-Saharan Africa (n=131) and Mayotte-Madagascar-Antilles-Caraibes-Guyane-Reunion (n=35) with n=65 and n-25 respectively. The phenotype C-c+E-e+ is the most retrieved with n=57 and n=25 respectively. Weak D type 1, 2 or 3 has been detected only in the Caucasians population.Conclusion: The population of North Africa presents significant differences with the Caucasian population. A similarity of distribution of polymorphisms was highlighted between the population of Sub-Saharan Africa and Mayotte-Madagascar-Antilles-Guyane-Réunion.It would be interesting to make a study on the gene D weak on a bigger samples to adapt the strategy of care for the patients who carries D weak 1, 2 and 3.; Objectifs : Étudier la population présentant un polymorphisme du rhésus D en région PACA-Corse-Monaco et corréler le D faible à une catégorie de population.Matériel et Méthodes : Une étude descriptive, des polymorphismes découverts lors du génotypage fœtal sur sang maternel au sein du laboratoire de biochimie et de biologie moléculaire de l’hôpital Nord, a été réalisée de 2008 à 2014. Au total 464 patientes décrites selon trois données qualitatives : origine géographique maternelle, phénotype maternel et génotype maternel. Pour répondre au second objectif, 34 patientes ont étédécrites sur les années 2013-2014.Résultats : Chez les Caucasiens (n=183) il a été retrouvé une majorité de RHD faibles/partiels (n=108) et C+c+E-e+ est le phénotype prédominant (n=122). Pour l’Afrique du Nord (n=131) il a été retrouvé une majorité d’hybrides (n=54) et le phénotype le plus retrouvé est C-c+E-e+ (n=61). Chezpatientes d’Afrique Subsaharienne (n=110) et Mayotte-Madagascar-Antilles-Caraibes-Guyane- Réunion (n=35), le pseudogène est prédominant avec respectivement n=65 et n=25. Le phénotype C-c+E-e+ est le plus fréquent avec n=57 et n=25.Les 3 types de D faibles génotypés (1, 2 et 3) ontété retrouvés seulement chez les Caucasiens.Conclusion : La population d’Afrique du Nord présente des différences significatives avec la population Caucasienne. Une similarité de répartition des polymorphismes a été mise en évidence entre la population d’Afrique Subsaharienne et Mayotte-Madagascar-Antilles-Guyane-Réunion. Il serait intéressant d’entreprendre une étude sur le gène D faible sur une plus grande cohorte afin d’adapter la stratégie de soin des patientes porteuses de D faibles type 1, 2 et 3.