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Cornelia de Lange syndrome ( CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin-related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of 11 patients carrying 10 distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS-overlapping features. The phenotype of our patients is very broad, whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X-inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counseling and risk prediction. [ABSTRACT FROM AUTHOR]

The two Cape hake species of the southern Benguela ecosystem, the shallow-water and deep-water hakes Merluccius capensis and M. paradoxus, are economically the most important marine resources in South Africa. Recruitment is a key process in the dynamics of marine organisms, yet very little is known about the early life history of Cape hakes, especially the location of spawning grounds and transport of eggs and larvae. For each species, ichthyoplankton dispersal off South Africa is simulated by coupling oceanographic simulations to an individual-based model in order to track virtual individuals. Results indicate that the most favorable spawning areas for transport to nursery areas are located off the south-western coast and the eastern Agulhas Bank, and highlight partly different drift routes followed by the two ichthyoplankton species off Cape Columbine. Transport from spawning to nursery areas is the highest in austral winter for a spawning depth ranging between 0 and 100 m. These modeling results are in broad agreement with available knowledge on the ecology of Cape hakes. The present work on Cape hakes complements previous modeling studies on anchovy and sardine in the same area. Taken together, these studies underline the correspondence between cross-shore (for hakes) or alongshore (for anchovy and sardine) transport mechanisms and the spawning strategies used by these key species of the southern Benguela ecosystem. [ABSTRACT FROM PUBLISHER]

Megalencephaly (MEG), or enlargement of the brain, can either represent a familial variant with normal cerebral structure, or a rare brain malformation associated with developmental delay and neurological problems. MEG has been split into two subtypes: anatomical and metabolic. The latter features a build-up inside the cells owing to metabolic causes. Anatomical MEG has been detected in many different conditions, including many overgrowth syndromes. In 2004 Mirzaa et al. reported five non-consanguineous patients with a new MCAJMR syndrome characterized by severe congenital MEG with polymicrogyria (PMG), postaxial polydactyly (POLY) and hydro-cephalus (HYD). The authors argued that these findings identified a new and distinct malformation syndrome, which they named MPPH. We report on a new case of MPPH, the first to be described after the original series (Mirzaa et al., 2004). [ABSTRACT FROM AUTHOR]

The article presents a case report which describes a 5-month-old boy with a Pallister-Killian syndrome (PKS), which is a dysmorphic condition caused by a tissue limited mosaicism for tetrasomy of 12p. A dermatologic examination of the skin by Wood's lamp had described that he had the typical PKS phenotype. Fluorescence in situ hybridization analysis of skin fibroblasts detected a supernumerary isochromosome 12p and confirmed the diagnosis of PKS.

The assessment of the mechanisms and patterns of larval connectivity between geographically separated populations leads to a better understanding of benthic marine population dynamics, especially in commercially valuable species. This study investigated for the first time the fine-scale temporal genetic variability of new settlers and their origins in a benthic marine organism with one of the longest pelagic larval phases, the Caribbean spiny lobster (Panulirus argus). We genotyped newly settled postlarvae in the Florida Keys and adults of spiny lobster from the Florida Keys and throughout the Caribbean Sea. We identified strong larval connectivity between Dominican Republic, Belize, Nicaragua, the Florida Keys, and West-Florida. The larval dispersal modeling suggests that Florida's lobster population could receive recruits from within and from other areas outside its state and national maritime boundaries. The genetic analyses refine the oceanographic model indicating that the connectivity patterns described could also result from unknown parental populations sourcing adults and postlarvae in different spawning seasons to the Florida Keys. We discuss the importance of small temporal scales to identify patterns in larval export. Our findings are significant on two levels. From the larval dispersal perspective, genetic results and biophysical modeling identify patterns of gene flow enhancing persistence of local populations. From an economic and fishery perspective, P. argus is the most important commercial species in the Caribbean and our results inform how considering larval source and sink dynamics across international boundaries could improve management plans at local, national, and regional levels. [ABSTRACT FROM AUTHOR]

Background: Since 2010, array-CGH (aCGH) has been the first-tier test in the diagnostic approach of children with neurodevelopmental disorders (NDD) or multiple congenital anomalies (MCA) of unknown origin. Its broad application led to the detection of numerous variants of uncertain clinical significance (VOUS). How to appropriately interpret aCGH results represents a challenge for the clinician. Method: We present a retrospective study on 293 patients with age range 1 month - 29 years (median 7 years) with NDD and/or MCA and/or dysmorphisms, investigated through aCGH between 2005 and 2016. The aim of the study was to analyze clinical and molecular cytogenetic data in order to identify what elements could be useful to interpret unknown or poorly described aberrations. Comparison of phenotype and cytogenetic characteristics through univariate analysis and multivariate logistic regression was performed. Results: Copy number variations (CNVs) with a frequency < 1% were detected in 225 patients of the total sample, while 68 patients presented only variants with higher frequency (heterozygous deletions or amplification) and were considered to have negative aCGH. Proved pathogenic CNVs were detected in 70 patients (20.6%). Delayed psychomotor development, intellectual disability, intrauterine growth retardation (IUGR), prematurity, congenital heart disease, cerebral malformations and dysmorphisms correlated to reported pathogenic CNVs. Prematurity, ventricular septal defect and dysmorphisms remained significant predictors of pathogenic CNVs in the multivariate logistic model whereas abnormal EEG and limb dysmorphisms were mainly detected in the group with likely pathogenic VOUS. A flow-chart regarding the care for patients with NDD and/or MCA and/or dysmorphisms and the interpretation of aCGH has been made on the basis of the data inferred from this study and literature. Conclusion: Our work contributes to make the investigative process of CNVs more informative and suggests possible directions in aCGH interpretation and phenotype correlation. [ABSTRACT FROM AUTHOR]

The article presents a case study of a young female with dental features of focal dermal hypoplasia known as Goltz-Gorlin syndrome and ectodermal dysplasia (ED). It describes the oro-dental characteristics of the patient which manifest a rare disorder resembling ED and shows oro-dental findings such as microdontia, taurodontism, and peg-shaped teeth. It also discusses the multidisciplinary treatment of the patient for Goltz-Gorlin syndrome in ED.