Does δ-sarcoglycan-associated autosomal-dominant cardiomyopathy exist?

In this study we clinically and genetically characterize a consanguineous family with a homozygous novel missense mutation in the δ-sarcoglycan gene and a second δ-sarcoglycan mutation that has previously been reported to cause severe autosomal-dominant dilated cardiomyopathy. We identified a novel missense mutation in exon 6 (p.A131P) of the δ-sarcoglycan gene, which in a homozygous state leads to the clinical picture of a limb girdle muscular dystrophy. In four heterozygous carriers for the mutation, aged 3–64 years, a second sequence variant in exon 6 (p.S151A) of the δ-sarcoglycan gene was detected on the other allele. This second missense change had previously been reported to be responsible for fatal autosomal-dominant dilated cardiomyopathy at young age. Comprehensive clinical and cardiac investigation in all of the compound heterozygous family members revealed no signs of cardiomyopathy or limb girdle muscular dystrophy. Our findings demonstrate that, even in the presence of a second disease-causing mutation, the p.S151A mutation in the δ-sarcoglycan gene does not result in cardiomyopathy. This finding questions the pathological relevance of this sequence variant for causing familial autosomal-dominant dilated cardiomyopathy and thereby the role of the δ-sarcoglycan gene in general as a disease-causing gene for autosomal-dominant dilated cardiomyopathy.     

Managing Duchenne muscular dystrophy--the additive effect of spinal surgery and home nocturnal ventilation in improving survival

OBJECTIVES: To determine the long term survival in patients with Duchenne muscular dystrophy (DMD) following spinal surgery and nocturnal ventilation. STUDY DESIGN: A retrospective review of 100 consecutive patients born between 1970 and 1990 was conducted. RESULTS: Forty-seven patients had surgical spinal fusion, 27 were subsequently ventilated. Fourteen patients received ventilation only. Thirty-nine patients received neither intervention. The age at which ventilation was required correlated with the age at which ambulation was lost. Those who walked for longer were less likely to require spinal surgery. Mean vital capacity dropped from 1.4 to 1.13 L 1 year post-operatively. Patients having both spinal surgery and ventilation had a median survival of 30 years whereas those who were only ventilated survived to 22.2 years. CONCLUSION: Nocturnal ventilation improves survival in DMD. Spinal surgery does not increase forced vital capacity but in combination with nocturnal ventilation further improves median survival to 30 years.     

Evaluation of a threshold-based tri-axial accelerometer fall detection algorithm

Using simulated falls performed under supervised conditions and activities of daily living (ADL) performed by elderly subjects, the ability to discriminate between falls and ADL was investigated using tri-axial accelerometer sensors, mounted on the trunk and thigh. Data analysis was performed using MATLAB to determine the peak accelerations recorded during eight different types of falls. These included; forward falls, backward falls and lateral falls left and right, performed with legs straight and flexed. Falls detection algorithms were devised using thresholding techniques. Falls could be distinguished from ADL for a total data set from 480 movements. This was accomplished using a single threshold determined by the fall-event data-set, applied to the resultant-magnitude acceleration signal from a tri-axial accelerometer located at the trunk.     

Guidelines for care of contact dermatitis

These guidelines for the management of contact dermatitis have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines, including details of relevant epidemiological aspects, diagnosis and investigation.     

A qualitative exploration of mothers' and fathers' experiences of having a child with Klinefelter syndrome and the process of reaching this diagnosis

Klinefelter syndrome (KS) is a common genetic condition that is currently under-diagnosed. The phenotype is broad, with physical, medical and psychosocial features ranging from mild to severe. When a child is diagnosed with KS, the parents may spend months to years searching for a diagnosis. This study used a qualitative methods approach to explore parents'' experiences of having a child with KS and receiving a diagnosis. Fifteen semistructured one-to-one in-depth interviews were conducted to explore their experiences and views. The interviews were then transcribed, coded and thematically analysed. The interviews revealed that parents had diverse experiences related to: the timing of the diagnosis of their child and reasons why their child was investigated for KS; the information that was provided at the time of diagnosis; the supports that were available and the concerns that parents held for the future of their child. The conclusions from this study were that parents'' experiences of having a child with KS and receiving a diagnosis were complex and multifaceted. This experience was shaped by the timing of when the diagnosis was received, who provided the diagnosis, what information was provided from health-care professionals and that which parents may have encountered on the internet. The long-term experiences for parents were also impacted by the level of support they received. These findings have implications for the process by which KS is recognised by the health-care community and supports available for families.     

UMOD as a susceptibility gene for end-stage renal disease

ABSTRACT: BACKGROUND: In recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant. METHODS: To investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls. After transplantation, 1066 renal transplant recipients were followed up for GF. Urinary uromodulin concentration was measured at median [IQR] 4.2 [2.2-6.1] yrs after kidney transplantation. RESULTS: The rs12917707 minor allele showed association with lower risk of ESRD (OR 0.89 [0.76-1.03], p = 0.04) consistent in effect size and direction with the previous report (Boger et al, PLoS Genet 2011). Meta-analysis of these findings showed significant association of rs12917707 with ESRD (OR 0.91 [0.85-98], p = 0.008). In contrast, rs12917707 was not associated with incidence of GF. Urinary uromodulin concentration was lower in recipient-carriers of the donor rs12917707 minor allele as compared to non-carriers, again consistent with previous observations in general population cohorts. CONCLUSIONS: Our study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.     

HISTOLOGICAL COMPARISON OF THE THIRD INTERDIGITAL NERVE IN PATIENTS WITH MORTON'S METATARSALGIA AND CONTROL PATIENTS

This study compares the histology of the plantar-digital nerve supplying the third web space in asymptomatic patients with those who have clinically diagnosed Morton's metatarsalgia. Despite several studies concentrating on the histological changes in the interdigital nerve, the relevance of these changes is a matter of contention while the exact pathological process responsible for the symptoms has not been determined. The histological findings in control patients were identical to Morton's patients with the exception of demyelination, which was more common in the Morton's group. This suggests that the characteristic nodule and fibrotic changes seen in the interdigital nerves of patients with Morton's neuroma cannot account for the symptoms and that the changes seen in the neurovascular bundle are degenerative in origin and are found in asymptomatic patients.