Mesoscale fluvial erosion parameters deduced from modeling the Mediterranean sea level drop during the Messinian (late Miocene)

International audienceAfter a base level drop, rivers are the first components of the landscape to respond by incising into topography. A base level drop results in a knickpoint in the downstream part of river longitudinal profiles. Whether knickpoints are preserved or erased during the upstream propagation of incision is still debated. Preservation and erasure of knickpoints are two end-member processes that work in natural systems at different timescales, different length scales, and different places. The huge (1500 m) and fast (tens of kiloyears) sea level drop in the Mediterranean during the Messinian resulted in the fast propagation of incision far inland. This is especially the case in the Rhone Valley (southern France) where the knickpoint is 300 km from the Mediterranean coast. Numerical modeling of this event has been performed using the ros model, which simulates both erosional and depositional processes in rivers. The best fit between numerical results and geological data is obtained for a nonlinear relation between incision and drainage area and for a small transport length of sediment. This small transport length, at least 2 orders of magnitude lower than the length of the Rhone, suggests that the longitudinal profile relaxed in a diffusive way, so that the initial knickpoint was not preserved. Finally, after a base level fall, the propagation of fluvial incision is very fast at geological timescales (hundreds of kiloyears). Despite this, the diffusive response implies that the time required for restoration of an equilibrium profile is very long

Utero-vaginal aplasia (Mayer-Rokitansky-Küster-Hauser syndrome) associated with deletions in known DiGeorge or DiGeorge-like loci

<p>Abstract</p> <p>Background</p> <p>Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part of the vagina in women showing normal development of secondary sexual characteristics and a normal 46, XX karyotype. The uterovaginal aplasia is either isolated (type I) or more frequently associated with other malformations (type II or Müllerian Renal Cervico-thoracic Somite (MURCS) association), some of which belong to the malformation spectrum of DiGeorge phenotype (DGS). Its etiology remains poorly understood. Thus the phenotypic manifestations of MRKH and DGS overlap suggesting a possible genetic link. This would potentially have clinical consequences.</p> <p>Methods</p> <p>We searched DiGeorge critical chromosomal regions for chromosomal anomalies in a cohort of 57 subjects with uterovaginal aplasia (55 women and 2 aborted fetuses). For this candidate locus approach, we used a multiplex ligation-dependent probe amplification (MLPA) assay based on a kit designed for investigation of the chromosomal regions known to be involved in DGS.</p> <p>The deletions detected were validated by Duplex PCR/liquid chromatography (DP/LC) and/or array-CGH analysis.</p> <p>Results</p> <p>We found deletions in four probands within the four chromosomal loci 4q34-qter, 8p23.1, 10p14 and 22q11.2 implicated in almost all cases of DGS syndrome.</p> <p>Conclusion</p> <p>Uterovaginal aplasia appears to be an additional feature of the broad spectrum of the DGS phenotype. The DiGeorge critical chromosomal regions may be candidate loci for a subset of MRKH syndrome (MURCS association) individuals. However, the genes mapping at the sites of these deletions involved in uterovaginal anomalies remain to be determined. These findings have consequences for clinical investigations, the care of patients and their relatives, and genetic counseling.</p

Phenotypic spectrum of fetal Smith-Lemli-Opitz syndrome.

International audienceThe Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive multiple congenital malformation syndrome caused by dehydrocholesterol reductase deficiency. The diagnosis is confirmed by high 7- and secondarily 8-dehydrocholesterol levels in plasma and tissues and/or by detection of biallelic mutations in the DHCR7 gene. The phenotypic spectrum of SLOS is broad, ranging from a mild phenotype combining subtle physical anomalies with behavioral and learning problems, to a perinatally lethal multiple malformations syndrome. The fetal phenotype of SLOS has been poorly described in the literature. We report a series of 10 fetuses with molecularly proven SLOS. Even in young fetuses, the facial dysmorphism appears characteristic. Genital abnormalities are rare in 46,XX subjects. Gonadal differentiation appears histologically normal and in agreement with the chromosomal sex, contrary to what has been previously stated. We observed some previously unreported anomalies: ulnar hypoplasia, vertebral segmentation anomalies, congenital pulmonary adenomatoid malformation, fused lungs, gastroschisis, holomyelia and hypothalamic hamartoma. This latter malformation proves that SLOS phenotypically overlaps with Pallister-Hall syndrome which remains clinically a major differential diagnosis of SLOS

Fifteen years of research on oral–facial–digital syndromes: from 1 to 16 causal genes

Oral–facial–digital syndromes (OFDS) gather rare genetic disorders characterised by facial, oral and digital abnormalities associated with a wide range of additional features (polycystic kidney disease, cerebral malformations and several others) to delineate a growing list of OFDS subtypes. The most frequent, OFD type I, is caused by a heterozygous mutation in the OFD1 gene encoding a centrosomal protein. The wide clinical heterogeneity of OFDS suggests the involvement of other ciliary genes. For 15 years, we have aimed to identify the molecular bases of OFDS. This effort has been greatly helped by the recent development of whole-exome sequencing (WES). Here, we present all our published and unpublished results for WES in 24 cases with OFDS. We identified causal variants in five new genes (C2CD3, TMEM107, INTU, KIAA0753 and IFT57) and related the clinical spectrum of four genes in other ciliopathies (C5orf42, TMEM138, TMEM231 and WDPCP) to OFDS. Mutations were also detected in two genes previously implicated in OFDS. Functional studies revealed the involvement of centriole elongation, transition zone and intraflagellar transport defects in OFDS, thus characterising three ciliary protein modules: the complex KIAA0753-FOPNL-OFD1, a regulator of centriole elongation; the Meckel-Gruber syndrome module, a major component of the transition zone; and the CPLANE complex necessary for IFT-A assembly. OFDS now appear to be a distinct subgroup of ciliopathies with wide heterogeneity, which makes the initial classification obsolete. A clinical classification restricted to the three frequent/well-delineated subtypes could be proposed, and for patients who do not fit one of these three main subtypes, a further classification could be based on the genotype

How did the Messinian Salinity Crisis end?

The cause of the desiccation of the Mediterranean Sea during the Messinian Salinity Crisis has been widely debated, but its re-flooding remains poorly investigated. Interpretations generally involve tectonic collapse of the Strait of Gibraltar or global sealevel rise, or even a combination of both. The dramatic sea-level fall in the Mediterranean has induced deep fluvial incision all around the desiccated basin. We investigate erosion dynamics related to this base level drop by using the numerical simulator EROS. We show that intense regressive erosion develops inevitably in the Gibraltar area eventually inducing the piracy of the Atlantic waters by an eastward-flowing stream and the subsequent re-flooding of the Mediterranean

Dynamique de l'érosion fluviatile consécutive à une chute du niveau de base (l'exemple de la crise de salinité messinienne)

Les variations du niveau de base entraînent une perturbation de la dynamique érosive d'un système continental. Une chute du niveau de base se traduit par la propagation d'une incision fluviatile vers l'amont entraînant un rajeunissement du paysage. Cette étude a pour but de montrer comment cette érosion affecte l'évolution d'un paysage, suivant les paramètres du système morphologique préexistant. Elle s'appuie sur un exemple préservé de chute du niveau de base de grande ampleur pendant la Crise de Salinité Messinienne en Méditerranée il y a 5.5 Ma. L'étude morphologique des incisions messiniennes couplée à une modélisation numérique montre qu'il existe une dichotomie entre la vitesse de croissance d'un réseau et ses effets sur l'évolution à long terme d'un paysage en présence d'une pente régionale préexistante. L'absence de pente régionale peut conduire à une modification drastique comme la capture de l'Atlantique au niveau de Gibraltar qui a entraîné la fin de la Crise Messinienne.RENNES1-BU Sciences Philo (352382102) / SudocPARIS-Museum-Bib. de géologie (751055215) / SudocSudocFranceF

Did the Ebro basin connect to the Mediterranean before the Messinian salinity crisis?

International audienceThe connection of the Ebro basin via the Ebro River to the Mediterranean Sea is supposed to have played a major role in the rejuvenation of relief of northern Spain and especially of the South Pyrenees from the Neogene by lowering the initial base level of the Ebro internal drainage area down to sea level. However, the timing and causes of this connection are still debated. A fundamental issue is whether the Ebro basin became connected to the Mediterranean before or after the Messinian salinity crisis? Morphological analysis and numerical modeling of landscape evolution show that this connection did not exist before the Messinian salinity crisis but is effective from the Pliocene because of progressive regressive erosion

Chorioamnionitis following preterm premature rupture of membranes and fetal heart rate variability

International audienceINTRODUCTION: The objective of this study was to identify prenatal markers of histological chorioamnionitis (HC) during pPROM using fetal computerized cardiotocography (cCTG). MATERIALS AND METHODS: Retrospective review of medical records from pregnant women referred for pPROM between 26 and 34 weeks, in whom placental histology was available, in a tertiary level obstetric service over a 5-year period. Fetal heart rate variability was assessed using cCTG. Patients were included if they were monitored at least six times in the 72 hours preceding delivery. Clinical and biological cCTG parameters during the pPROM latency period were compared between cases with or without HC. RESULTS: In total, 222 pPROM cases were observed, but cCTG data was available in only 23 of these cases (10 with and 13 without HC) after exclusion of co-morbidities which may potentially perturb fetal heart rate variability measures. Groups were comparable for maternal age, parity, gestational age at pPROM, pPROM duration and neonatal characteristics (p>0.1). Baseline fetal heart rate was higher in the HC group [median 147.3 bpm IQR (144.2-149.2) vs. 141.3 bpm (137.1-145.4) in no HC group; p = 0.02]. The number of low variation episodes [6.4, (3.5-15.3) vs. 2.3 (1-5.2); p = 0.04] was also higher in the HC group, whereas short term variations were lower in the HC group [7.1 ms (6-7.4) vs. 8.1 ms (7.4-9); p = 0.01] within 72 hours before delivery. Differences were especially discriminant within 24 hours before delivery, with less short-term variation [5 ms (3.7-5.9) vs. 7.8 ms (5.4-8.7); p = 0.007] and high variation episodes [3.9 (4.9-3.2) vs. 0.8 (1.5-0.2); p < 0.001] in the HC group. CONCLUSION: These results show differences in fetal heart rate variability, suggesting that cCTG could be used clinically to diagnoses chorioamnionitis during the pPROM latency period

Genetic counseling and "molecular" prenatal diagnosis of holoprosencephaly (HPE).

International audienceHoloprosencephaly (HPE) is a structural anomaly of the developing brain in which the forebrain fails to divide into two separate hemispheres and ventricles. The poor prognosis in the most severe forms justifies the importance of genetic counseling in affected families. The genetic counseling requires a thorough clinical approach given the extreme variability of phenotype and etiology. The karyotype is an essential diagnostic tool. Since mutations in the four major genes (SHH, ZIC2, SIX3, and TGIF) have been identified in HPE patients, molecular study is performed routinely in nonsyndromic HPE. New molecular tools, such as array-CGH analysis, are now part of the diagnostic process. Prenatal diagnosis is based primarily on fetal imaging, but "molecular" prenatal diagnosis can be performed if a mutation has been previously identified in a proband. Interpretations of molecular diagnosis must be given with caution, given the lack of strict genotype-phenotype correlation, and should be offered in addition to fetal imaging, using ultrasound followed by fetal MRI. We report on our experience of 15 molecular prenatal diagnoses from chorionic villi or amniotic fluid sampling. In eight instances, we were able to reassure the parents after taking into account the absence of the mutation in the fetus, previously identified before in a parent and/or a proband. Fetal RMI was normal later in pregnancy, and no child had medical problems after birth. The mutation was found in the seven other cases: four children were born, either without brain malformation and asymptomatic, or had a less severe form than the index case

Elucidating in utero fetal demise time to reassemble the pieces of the puzzle?

International audienc