Neurobehavioral phenotype in carriers of the fragile X premutation

There have been contradictory findings in the fragile X (fraX) literature about possible neurocognitive and psychological symptoms due to the fraX premutation (pM). The purpose of the present study was to investigate the relationship between CGG repeat length and neurobehavioral functioning in carriers of the fraX pM. Eighty‐five female carriers of the pM with allele sizes ranging from 59–166 were administered a comprehensive IQ test (WAIS‐III) and completed a questionnaire designed to measure psychopathology (Symptom Checklist (SCL)‐90‐R). No relationship between allele size and cognition was identified. A significant negative relationship between allele size and age was found, as well as a positive relationship between allele size and depression. Follow‐up analyses separating small and large allele sizes (below and above 100 CGG repeats) indicated that individuals with larger allele sizes scored significantly higher on the Interpersonal Sensitivity and Depression subscales of the SCL‐90‐R. Despite the limitation of few individuals with high CGG repeat lengths, our findings suggest that females with larger premutated alleles (≥ 100 repeats) display some clinical manifestations of fraX syndrome. © 2001 Wiley‐Liss, Inc.     

Utilization of the 2017 diagnostic criteria for hEDS by the Toronto GoodHope Ehlers–Danlos syndrome clinic: A retrospective review

The new 2017 diagnostic criteria for hypermobile Ehlers–Danlos Syndrome (hEDS) provide a framework for diagnosing hEDS but are more stringent than the previous Villefranche criteria. Our clinical experience at the GoodHope EDS clinic was that the 2017 criteria left many highly symptomatic patients without a diagnosis of hEDS. We conducted a retrospective cohort study to confirm our clinic experience and assess the accuracy of the 2017 diagnostic criteria for hEDS in patients who had a previous hEDS diagnosis based on the Villefranche criteria. Our study found that 15% (n = 20 of 131) of patients with a prior diagnosis of hEDS met the 2017 diagnostic criteria, and many of the traits used to distinguish hEDS were not significantly more frequent in patients who met 2017 criteria versus those who did not. In both groups objective systemic manifestations were found less frequently than subjective systemic manifestations. Beighton score (BS) as assessed by primary care practitioner was found to be higher than assessment by EDS practitioner in 81% (n = 74 of 91) of cases. Generalized joint hypermobility was confirmed in only 46% (n = 51 of 111) of patients who had a previous diagnosis of hEDS. Higher BS did not correlate with increased number of systemic manifestations in our cohort. Common comorbidities of hEDS were found with similar frequency in those who met 2017 criteria and those who did not. Based on our cohort, the 2017 hEDS diagnostic criteria require refinement to improve its diagnostic accuracy.     

Origin of Fueguian‐Patagonians: An approach to population history and structure using R matrix and matrix permutation methods

A complicated history of isolation between Fueguian and Patagonian groups (originated by the appearance of the Straits of Magellan) as much as differences in population structure and life strategies constitute important factors in the clustering pattern of those groups. The aim of this work was to test several hypotheses about population structure and history of Fueguian‐Patagonians to propose a model that incorporates predictions for future studies. R matrix methods and matrix permutation analyses were performed upon a data matrix of craniofacial measurements of 441 skulls divided into nine samples pertaining to six Patagonian and three Fueguian populations. Association of biological distances with three matrices representing several settlement patterns was tested using matrix permutation tests. Results of R matrix study show that the minimum genetic distance obtained confirms separation between Fueguians and Patagonians. Moreover, an analysis of residual variances from the expected regression line confirms admixture between Andean and Pampean populations and Araucanian groups, consistent with ethnohistorical observations. A model representing a long history of isolation between Fueguian and Patagonians, rather than a model emphasizing differences in life‐strategies, presented the best correlation with the biological distance matrix. Because similar results were already obtained in archaeological, molecular, and morphological studies, a model for the settlement of Tierra del Fuego is proposed. It is summarized by four main hypotheses that can be tested independently by different disciplines in the future. Am. J. Hum. Biol. 14:308–320, 2002. © 2002 Wiley‐Liss, Inc.     

Nkx2.5‐negative myocardium of the posterior heart field and its correlation with podoplanin expression in cells from the developing cardiac pacemaking and conduction system

Recent advances in the study of cardiac development have shown the relevance of addition of myocardium to the primary myocardial heart tube. In wild‐type mouse embryos (E9.5–15.5), we have studied the myocardium at the venous pole of the heart using immunohistochemistry and 3D reconstructions of expression patterns of MLC‐2a, Nkx2.5, and podoplanin, a novel coelomic and myocardial marker. Podoplanin‐positive coelomic epithelium was continuous with adjacent podoplanin‐ and MLC‐2a‐positive myocardium that formed a conspicuous band along the left cardinal vein extending through the base of the atrial septum to the posterior myocardium of the atrioventricular canal, the atrioventricular nodal region, and the His‐Purkinje system. Later on, podoplanin expression was also found in the myocardium surrounding the pulmonary vein. On the right side, podoplanin‐positive cells were seen along the right cardinal vein, which during development persisted in the sinoatrial node and part of the venous valves. In the MLC‐2a‐ and podoplanin‐positive myocardium, Nkx2.5 expression was absent in the sinoatrial node and the wall of the cardinal veins. There was a mosaic positivity in the wall of the common pulmonary vein and the atrioventricular conduction system as opposed to the overall Nkx2.5 expression seen in the chamber myocardium. We conclude that we have found podoplanin as a marker that links a novel Nkx2.5‐negative sinus venosus myocardial area, which we refer to as the posterior heart field, with the cardiac conduction system. Anat Rec, 290:115–122, 2007. © 2006 Wiley‐Liss, Inc.     

Neuropsychological functions,sleep, and mental health in adults with Klinefelter syndrome

A few studies have examined neuropsychological functions, sleep, and mental health combined in Klinefelter syndrome (KS; 47,XXY). We investigated neuropsychological functions with standard tests, sleep with actigraphy, and self‐reported mental health in 30 men with KS (Mean age = 36.7 years) compared to 21 controls (Mean age = 36.8 years). Men with KS scored significantly lower on mental speed, attention span, working memory, inhibition, and set‐shifting tests, as well as overall IQ (mean effect size difference Cohen's d = 0.79). Men with KS had significantly longer night wakes, with no differences in other sleep variables (mean d = 0.34). Men with KS reported poorer mental health than controls (mean d = 1.16). Regression analyses showed neuropsychological functions explained variance in some sleep domains for men with KS but not for controls. Neuropsychological functions explained variance in some mental health domains for controls. For men with KS, however, verbal IQ was the only significant predictor of mental health. Altogether, men with KS display problems in neuropsychological functions and mental health but do not appear different from controls on most sleep parameters. Our findings indicate that relations between neuropsychological functions, sleep, and mental health differ between men with KS and controls.     

Complementary DNA sequence of the HLA‐B*3924 allele1

We have isolated the complete coding region of HLA‐B*39 from a Spanish Caucasoid, using a new PCR primer for its 5′ untranslated region. The cDNA matched partial genomic sequences of B*3924, an allele whose distribution appears to be restricted to Mediterranean and Arabian Caucasoids. A single amino acid change exclusive to B*3924 (threonine‐98) distinguishes it from B*3903.     

Coagulopathy of massive transfusion: pathophysiology and monitoring

Coagulopathy associated with massive transfusion (MT) remains an important clinical problem. The author attempted to identify the causes of coagulopathy in massively transfused, adult and previously haemostatically competent patients and to differentiate between the elective surgical and the emergency settings. A MEDLINE search was conducted for articles published on ‘massive transfusion’, ‘transfusion’, ‘trauma’, ‘surgery’, ‘coagulopathy’ and ‘haemostatic defects’. A narrative format was adopted. Coagulopathy associated with MT is an intricate, multifactorial and multicellular event. In patients undergoing elective surgery, a decrease in fibrinogen concentration is observed initially while thrombocytopenia is a late occurrence. Critically low levels of coagulation factors were seldom reported when whole blood was in common use. With the use of packed red blood cells (PRBC), dilution or consumption of coagulation factors has become a significant issue requiring specific treatment with, primarily, fresh frozen plasma (FFP). In the emergency setting (e.g., trauma, ruptured abdominal aortic aneurysm), tissue trauma, shock, tissue anoxia and hypothermia contribute to the development of disseminated intravascular coagulation and microvascular bleeding. It has been shown that the proactive administration of platelets and FFP improves coagulation, decreases haemorrhage and improves survival in these massively bleeding patients. We can only speculate that in this specific context, the benefits of early and aggressive platelet and coagulation factor replacement are related to the ongoing consumption coagulopathy at the time of surgery.