Novel TMC8 splice site mutation in epidermodysplasia verruciformis and review of HPV infections in patients with the disease.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a genodermatosis leading to infections with cutaneous HPV, persistent plane warts and a high rate of non-melanoma skin cancer (NMSC). Biallelic loss-of-function mutations in TMC6 and TMC8 are known to be causative. OBJECTIVE: The aim of this study was to report EV-causing mutations in four patients with EV and to give an overview of all described patients with EV. PATIENTS AND METHODS: We investigated four patients with classical features of EV from two families. All patients were affected by plane warts with typical EV histology since early childhood, and ß-HPVs were detected on their skin. One patient had recurring cutaneous squamous cell carcinomas (cSCC) and carcinomas in situ (Bowen type). We sequenced both TMC6/8 for disease-causing mutations and quantified levels of gene expression. We also performed a systematic literature review to discuss these patients in the context of previously reported cases, mutations already identified, as well as HPV types. RESULTS: Three patients of one family carried a homozygous splice site mutation in TMC8 resulting in aberrantly spliced transcripts that were not degraded. By contrast, no TMC6/8 mutation was detected in the patient from the other family. A systematic literature review revealed 501 described patients with EV. Around 40% of patients with EV analysed for genetic alterations carried no mutation in TMC6/8. While ß-HPVs were identified in the majority of cases, α-HPVs were detected in several individuals. CONCLUSION: The relatively high proportion of EV patients without mutation in TMC6/8 indicates the existence of EV-causing mutations in additional, presently unknown gene(s). However, a homozygous TMC8 splice site mutation in our patients resulted in aberrant transcripts which cannot retain the healthy phenotype. The literature review revealed that HPV-5 is the most commonly identified HPV in patients with EV, but HPV-3, HPV-14 and HPV-20 were unexpectedly identified more frequently than HPV-8.

Early onset marfan syndrome: Atypical clinical presentation of two cases.

Early onset Marfan Syndrome (eoMFS) is a rare, severe form of Marfan Syndrome (MFS). The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system.

Tricho-rhino-phalangeal syndrome type 1 as an outcome of in vitro fertilization?

Trichorhinophalangeal syndrome type I [OMIM #190350] is an autosomal dominant disorder. Common features are: Slowly growing sparse hair, laterally thin eyebrows, bulbous tip of the nose, long philtrum, thin upper lip, protruding ears. Common skeletal anomalies include shortening of phalanges and metacarpals causing mild to severe brachydactyly, cone shaped epiphyses, hip dysplasia and short stature. Recently many reports have been published on the use of assisted reproductive technology (ART) and the increased risk of congenital major malformations or syndromes. We present a 6 years old Turkish Trichorhinophalangeal syndrome (TRPS) case of a twin pair after in vitro fertilization (IVF). TRPS with IVF pregnancy has not been reported previously. This new case reported herein will contribute to a better understanding whether ART pregnancy increases congenital malformations.

Partial trisomies of 8q and 15q due to maternal balanced translocations.

Unbalanced translocation involving both chromosomes 8q and 15q trisomies are extremely rare events. We present two different cases with unbalanced chromosomal rearrangements both derived from maternal balanced translocations. The first case is a 4 year-old boy with speech delay, dysmorphic facial features (inc. cleft lip/palate), behavioural disturbances and growth retardation, who had partial 8q trisomy and partial 21p monosomy resulting from a maternal t(8;21) reciprocal translocation. The other case is a 2 day-old boy with ventriculomegaly, dysmorphic facial features and heart defects (patent ductus arteriosus and atrial septal defect) who had partial 15q trisomy and partial 9p monosomy resulting from a maternal t(9;15) reciprocal translocation.

Acute liver failure in a metropolitan area in Germany: a retrospective study (2002 - 2008).

OBJECTIVES: To determine current etiologies of acute liver failure (ALF) and clinical and laboratory parameters associated with the outcome upon ALF, so as to identify the frequency of present causes of ALF in Germany as well as potential new prognostic parameters. PATIENTS: 134 adult patients (63 % females / 37 % males) aged 41 +/- 16 years (median: 38 years) with established ALF criteria. DESIGN AND SETTING: A retrospective study (1 / 2002 - 4 / 2008) on ALF patients from the Ruhr Area, the largest urban region located in northwestern Germany. Clinical and laboratory data were collected for a period of four weeks after study admission. RESULTS: Etiologies of ALF were identified as drug toxicity (39.6 % of the cases); combined viral hepatitides (23.1 %); or miscellaneous (16.4 %). In 20.9 % of the cases, the etiology remained indeterminate. Overall patient survival at four weeks was 81.3 %. While 89 patients (66.4 %) recovered under best supportive therapy, 26 patients (19.4 %) had to undergo liver transplantation. Increased body mass indices were significantly (p < 0.003) associated with a poor outcome. Intriguingly, high levels of cholestatic enzymes significantly (p < 0.01) correlated with a positive outcome. CONCLUSIONS: In providing first data on current ALF etiologies Germany, this study reveals that drug toxicity - in particular due to acetaminophen - has replaced viral hepatitis as the most single frequent cause of ALF in a densely populated urban area; this correlates with similar findings in the USA, the UK and Scandinavia. Lower body mass indices and elevated cholestatic enzyme levels had statistically significant prognostic power.

Comparative anatomy of the porcine and human thoracic spines with reference to thoracoscopic surgical techniques.

BACKGROUND: This study compared porcine and human thoracic spine anatomies for a better understanding of how structures encountered during thoracoscopy differ between training with a porcine model and actual surgery in humans. METHODS: Parameters were measured including vertebral body height, width, and depth; disc height; rib spacing; spinal canal depth and width; and pedicle height and width. RESULTS: Although most porcine vertebral structures were smaller, porcine pedicle height was significantly greater than that of humans because the porcine pedicle houses a unique transverse foramen. The longus colli and psoas attach, respectively, to T5 and T13 in swine and to T3 and T12 in humans. In swine, the azygos vein generally was absent. The intercostal veins drained into the hemiazygos vein. CONCLUSIONS: Several thoracoscopically relevant anatomic differences between human and porcine spinal anatomies were identified. A thoracoscopic approach in a porcine model probably is best performed from the right side. The best general working area is between T6 and T10.

Sieving effect of heat-denatured milk proteins during ultrafiltration of skim milk. I. The preliminary approach.

The effect of heat treatment of skim milk on the ultrafiltration process was examined. The change in permeate collection rate was explained as a function of heat-induced modifications of the milk protein system. It is suggested that there was a sieving effect which contributed to the acceleration of permeate flow-down during membrane filtration. It is thought that this resulted from formation of complex structures between heat-denatured whey proteins and casein micelles.

Lumbosacral neurenteric cyst with associated tethered cord in an adult.

Spinal neurenteric cysts are rare congenital lesions of endodermal origin that lead to spinal cord compression or tethering. These cysts are usually lined by mucus-secreting epithelium resembling that of the gastrointestinal tract. A 31-year-old man presented with low back and bilateral limb pain of three-year duration. Magnetic resonance imaging (MRI) revealed an intradural extramedullary heterogeneous mass lesion at L4 - L5 disc level causing severe compression and displacement of terminal portion of conus medullaris to the left side. Additionally, tethered cord, syringohydromyelia and spina bifida were present. He had also polysyndactyly on the left foot. The patient underwent laminoplasty and partial excision of the lesion through a posterior approach. Neurosurgical exploration revealed a large intradural, extramedullary solid lesion with cystic component, compressing the spinal cord. Histopathology confirmed a neurenteric cyst with mucin-producing cuboidal or columnar epithelium lining the cystic cavity. Clinical suspicion is important for an early diagnosis, and their early preplanned surgical removal should be the goal of treatment, which leads to a better outcome. This case is reported in view of rare congenital abnormality in an adult with peculiar presentation.