Hereditary multiple and isolated sporadic exostoses in the same kindred: identification of the causative gene (EXT2) and detection of a new mutation, nt112delAT, that distinguishes the two phenotypes

Hereditary multiple exostoses (HME) is a well known autosomal dominant hereditary orthopedic disorder. Isolated exostoses, on the other hand, occur as sporadic events or as secondary post-traumatic sequel. The occurrence of solitary exostoses in individuals from pedigrees affected with HME may distort conclusions about carrier status and/or diagnosis. Both conditions are potentially malignant and both are associated with genetic alterations in either EXT1 or EXT2 genes. In this study, we present a seven-generation family from western Sweden consisting of 170 blood relatives, 38 of whom had multiple cartilaginous exostoses, while 8 had isolated exostoses. Linkage analysis aimed to discern one of the known EXT genes demonstrated linkage of the HME phenotype to the EXT2 gene. Subsequent mutation analysis revealed a novel mutation, nt112delAT, in this gene. All carriers of the detected mutation had multiple exostoses, indicating full penetrance. None of the pedigree members with isolated exostoses were carriers of the detected mutation. Two of the mutation carriers developed chondrosarcoma yielding a 5.2% risk of malignant development for this mutation. The detection of this mutation has enabled us to provide appropriate genetic counseling concerning this complex situation.     

Immune-complex glomerulonephritis, intranuclear particles in hepatocytes, and in vivo clearance rates in sub-human primates inoculated with HBs AG-containing plasma.

Twelve subhuman primates [eight baboons (Papio anubis) and four rhesus (Macaca mulatta)] were inoculated with varying amounts of human plasma containing HB_s Ag with Dane particles. Serial blood specimens and liver, kidney, bone marrow, and lymph node biopsies were obtained from each animal over 10–12 mo. No measurable evidence of HB_s Ag production was observed in any animal after the initial clearance of antigen, although the presence of anti-HB_s in most of the animals studied might have precluded its detection. Two baboons developed progressive focal glomerulonephritis with mesangial alterations over a 4- to 10-mo period of time. Liver biopsies from these baboons and one rhesus monkey revealed the presence of 26-nm intranuclear particles in the hepatocytes at 4 mo postinoculation. The intranuclear particles were similar in morphology and in size to the cores of Dane particles. Kinetic analysis of antigen clearance implied a rapid uptake of HB_s Ag from the blood to the liver and spleen over an 8 to 24-hr period of time and an in vivo clearance rate ($\text{T}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$) of 28.2 hr.     

Interplay between chronic hepatitis B and atherosclerosis: Innovative perspectives and theories

Elaboration of carotid atherosclerosis in the setting of hepatitis B virus(HBV)infection should emphasize the significance of extrahepatic manifestations of the infection pathogenesis.Diverse processes comprise the pathoevolution of HBV infection,rendering it a multi-systemic disease in its essence.Our work not only exemplified atherosclerosis as an often-underestimated contributor to the severity of HBV infection but has also highlighted the bidirectional relationship between the two.Therefore,it is suggested that HBV-induced inflammation is one of the root causes of atherosclerosis,which in turn has a consequent effect on the severity of the chronic infection disease state,creating a vicious cycle.Additionally,we coupled prior data with the current concepts of HBV infection to postulate intriguing perspectives and theories.     

Correlation between procalcitonin and intra-abdominal pressure and their role in prediction of the severity of acute pancreatitis

Background/aimsEarly assessment of disease severity and vigilant patient monitoring are key factors for adequate treatment of acute pancreatitis (AP). The aim of this study was to determine the correlation of procalcitonin (PCT) serum concentrations and intra-abdominal pressure (IAP) as prognostic markers in early stages of AP.MethodsThis prospective observational study included 51 patients, of which 29 had severe AP (SAP). Patients were evaluated with the Acute Physiology And Chronic Health Evaluation (APACHE II) score, C-reactive protein (CRP) and PCT serum concentrations and IAP at 24 h from admission. PCT was measured three times in the 1st week of disease and three times afterward, while IAP was measured daily. PCT and IAP values correlated with each other, and also compared with APACHE II score and CRP values.ResultsPCT, IAP, CRP values and APACHE II score at 24 h after hospital admission were significantly elevated in patients with SAP. There was significant correlation between PCT and IAP values measured at 24 h of admission, and between maximal PCT and IAP values. Sensitivity/specificity for predicting AP severity at 24 h after admission was 89%/69% for APACHE II score, 75%/86% for CRP, 86%/63% for PCT and 75%/77% for IAP.ConclusionsIncreased IAP was accompanied by increased PCT serum concentration in patients with AP. PCT and IAP can both be used as early markers of AP severity.     

A case report of two male siblings with autism and duplication of Xq13–q21, a region including three genes predisposing for autism

Autism spectrum disorder, severe behaviour problems and duplication of the Xq12 to Xq13 region have recently been described in three male relatives. To describe the psychiatric comorbidity and dysmorphic features, including craniosynostosis, of two male siblings with autism and duplication of the Xq13 to Xq21 region, and attempt to narrow down the number of duplicated genes proposed to be leading to global developmental delay and autism. We performed DNA sequencing of certain exons of the TWIST1 gene, the FGFR2 gene and the FGFR3 gene. We also performed microarray analysis of the DNA. In addition to autism, the two male siblings exhibited severe learning disability, self-injurious behaviour, temper tantrums and hyperactivity, and had no communicative language. Chromosomal analyses were normal. Neither of the two siblings showed mutations of the sequenced exons known to produce craniosynostosis. The microarray analysis detected an extra copy of a region on the long arm of chromosome X, chromosome band Xq13.1–q21.1. Comparison of our two cases with previously described patients allowed us to identify three genes predisposing for autism in the duplicated chromosomal region. Sagittal craniosynostosis is also a new finding linked to the duplication.     

Renal bladder ultrasound evaluation in monosymptomatic primary nocturnal enuresis: is it really necessary?

Background

Published guidelines regarding radiographic imaging in the evaluation of monosymptomatic primary nocturnal enuresis (MPNE) are not followed. We aimed to evaluate the prevalence of urological abnormalities on renal/bladder ultrasound (RBUS) in children with MPNE and to compare the RBUS findings in children with and without MPNE.

Methods

Retrospective data collection in all children aged 5–17 years seen for the initial evaluation of MPNE. Control group consisted of age- and sex-matched children who had abdominal ultrasound for other than bladder-/kidney-related causes. RBUS findings were analyzed with regard to the need for intervention and/or follow-up.

Results

While abnormalities on RBUS were seen in 12.54 % of enuretic children and in 5.38 % of controls (p?=?0.004), the majority of these findings were clinically insignificant. Of those with abnormalities, only 4 enuretic children (1.43 %) required intervention and 8 (2.87 %) needed follow-up studies. These rates were not significantly different from the controls. However, enuretic children with RBUS abnormalities appear to be more resistant to treatment than enuretic children with normal RBUS (p?=?0.002).

Conclusions

A small proportion of abnormalities seen on RBUS in children with MPNE require intervention and/or further evaluation. The identification of insignificant RBUS findings could lead to unnecessary additional investigations owing to parental concern. Detailed history and a voiding diary may be sufficient in the initial evaluation of children with MPNE, although RBUS may play an important role in patients who are resistant to treatment.