Spherical parameterization for genus zero surfaces using Laplace-Beltrami eigenfunctions

International audienceIn this work, we propose a fast and simple approach to obtain a spherical parameterization of a certain class of closed surfaces without holes. Our approach relies on empirical findings that can be mathematically investigated, to a certain extent, by using Laplace-Beltrami Operator and associated geometrical tools. The mapping proposed here is defined by considering only the three first non-trivial eigenfunctions of the Laplace-Beltrami Operator. Our approach requires a topological condition on those eigenfunctions, whose nodal domains must be 2. We show the efficiency of the approach through numerical experiments performed on cortical surface meshes

Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism

To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability

Surface smoothing: a way back in early brain morphogenesis.

International audienceIn this article we propose to investigate the analogy between early cortical folding process and cortical smoothing by mean curvature flow. First, we introduce a one-parameter model that is able to fit a developmental trajectory as represented in a Volume-Area plot and we propose an efficient optimization strategy for parameter estimation. Second, we validate the model on forty cortical surfaces of preterm newborns by comparing global geometrical indices and trajectories of central sulcus along developmental and simulation time

The frequency of severe Fetal Alcohol Spectrum Disorders in the neonatal period using data from the French hospital discharge database between 2006 and 2013.

At birth, only complete Fetal Alcohol Syndrome (FAS) can be properly diagnosed. However, other Consequences of prenatal Alcohol Exposure (CAE) can also be recorded. Our objective was to describe the frequency of diagnoses highly suggestive of "potential Fetal Alcohol Syndrome Disorder" (pFASD, i.e., FAS and CAE) among hospitalized neonates, during the neonatal period, in France, between 2006 and 2013. We used the French national hospital discharge database to identify the Q86.0 (FAS) and P04.3 (CAE) ICD-10 codes in hospital stays occurring in the first 28 days of life. FAS, CAE and pFASD rates were estimated per 1000 live births at the national level for the 2009-2013 period. We compared the 2006-2009 and 2010-2013 rates. The pFASD rates were also estimated at the regional level. Overall, 3,207 cases of pFASD were diagnosed during the neonatal period (i.e., 0.48 cases per 1000 live births, including 0.07 cases of FAS per 1000). Between 2006-2009 and 2010-2013, pFASD remained stable, despite a moderate decrease in reported FAS (0.08 vs 0.06 cases per 1000, p < 0.001). At the regional level, pFASD rates varied between 0.13 and 1.22 cases per 1000. This study provides the first national estimate of neonatal diagnosis of FAS, and more broadly pFASD, in France. Although our data certainly underestimate the real prevalence of FASD, they provide a minimal estimate of the burden of alcohol use during pregnancy. Observed variations deserve to be analyzed in the light of concomitant prevention and public information campaigns

The Renpenning syndrome spectrum: new clinical insights supported by 13 new PQBP1-mutated males.

International audienceSince the first reports of polyglutamine-binding protein 1 (PQBP1) mutations in Renpenning syndrome and related disorders, the spectrum of PQBP1-linked clinical manifestations has been outlined from rare published case reports. The phenotypic description is often obtained from medical archives, and therefore, heterogeneous. Moreover, some aspects such as brain imaging or cognitive and behavioral functioning are rarely described. In this study, 13 PQBP1-mutated French patients were subjected to a standardized clinical, cognitive and behavioral assessment. Physical measurements of their relatives were also collected. We report on a recognizable clinical and radiological phenotype. All patients presented with microcephaly, leanness and mild short stature, relative to familial measurements. Three new clinical features are described: upper back progressive muscular atrophy, metacarpophalangeal ankylosis of the thumb and velar dysfunction. The specific facial dysmorphic features included at least four of the following signs: long triangular face, large ridged nose, half-depilated eyebrows, dysplastic or protruding ears and rough slightly sparse hair. An over-aged appearance was noticed in elderly patients. Cortical gyrification was normal based on available magnetic brain imaging of six patients. PQBP1-linked microcephaly (or Renpenning syndrome) is an X-linked mental retardation syndrome, which has clinically recognizable features

Simplified gyral pattern in severe developmental microcephalies? New insights from allometric modeling for spatial and spectral analysis of gyrification

The strong positive-allometric relationship between brain size, cortical extension and gyrification complexity, recently highlighted in the general population, could be modified by brain developmental disorders. Indeed, in case of brain growth insufficiency, the pathophysiological relevance of the "simplified gyral pattern" phenotype is strongly disputed since almost no genotype-phenotype correlations have been found in primary microcephalies. Using surface scaling analysis and newly-developed spectral analysis of gyrification (Spangy), we tested whether the gyral simplification in groups of severe microcephalies related to ASPM, PQBP1 or fetal-alcohol-syndrome could be fully explained by brain size reduction according to the allometric scaling law established in typically-developing control groups, or whether an additional disease effect was to be suspected. We found the surface area reductions to be fully explained by scaling effect, leading to predictable folding intensities measured by gyrification indices. As for folding pattern assessed by spectral analysis, scaling effect also accounted for the majority of the variations, but an additional negative or positive disease effect was found in the case of ASPM and PQBP1-linked microcephalies, respectively. Our results point out the necessity of taking allometric scaling into account when studying the gyrification variability in pathological conditions. They also show that the quantitative analysis of gyrification complexity through spectral analysis can enable distinguishing between even (predictable, non-specific) and uneven (unpredictable, maybe disease-specific) gyral simplifications

Severe neonatal hypercalcemia caused by subcutaneous fat necrosis without any apparent cutaneous lesion.

International audienceSubcutaneous fat necrosis is a classic, albeit uncommon, cause of neonatal hypercalcemia. It occurs in newborn infants within the first month of life following a complicated delivery. The diagnosis is usually easy because of the presence of red-purple plaques in fatty areas along with firm subcutaneous nodules. A 1-month-old neonate, born strangled by her umbilical cord, presented with diarrhea and hypercalcemia (3.46 mM) with an initial physical examination considered normal. Her biological evaluations were as follows: P = 1.37 mM (1.6-2.2); PTH = 3 ng/L (12-65); 25-OH vitamin D = 87 nM (23-113); (1,25)-OH(2) vitamin D = 192 ng/L (20-46). The third day, a careful exam of the whole cutaneous surface revealed small firm subcutaneous nodules in the ischial region. Despite the absence of any visible skin modification, the association of perinatal stress and high (1,25)-OH(2) vitamin D level with subcutaneous nodules led to the diagnosis of subcutaneous fat necrosis. She was treated with oral prednisone for 45 days. Serum calcium levels normalized within a week, and the nodules disappeared without complications. Conclusion: Subcutaneous fat necrosis may induce severe hypercalcemia without any visible cutaneous lesion