- [A clinical study of Proteus syndrome caused by a mosaic somatic mutation in AKT1 gene]. [Case Reports]
- ZNZhonghua Nei Ke Za Zhi 2019 Jul 01; 58(7):508-513
- CONCLUSIONS: The prominent features of Proteus syndrome are overgrowth of one extremity and cerebral connective tissue nevus. A mosaic somatic mutation of AKT1 gene is one of the pathogenic mutations for Proteus syndrome, and orthopedic surgery may be a good way to improve symptoms of the disease.
- Movement reveals reproductive tactics in male elephants. [Journal Article]
- JAJ Anim Ecol 2019 Jun 24
- Long-term bio-logging has the potential to reveal how movements, and hence life-history trade-offs, vary over a lifetime. Reproductive tactics in particular may vary as individuals' trade-off current…
Long-term bio-logging has the potential to reveal how movements, and hence life-history trade-offs, vary over a lifetime. Reproductive tactics in particular may vary as individuals' trade-off current investment versus lifetime fitness. Male African savanna elephants (Loxodona africana) provide a telling example of balancing body growth with reproductive fitness due to the combination of indeterminate growth and strongly delineated periods of sexual activity (musth), which results in reproductive tactics that alter with age. Our study aims to quantify the extent to which male elephants alter their movement patterns, and hence energetic allocation, in relation to (a) reproductive state and (b) age, and (c) to determine whether musth periods can be detected directly from GPS tracking data. We used a combination of GPS tracking data and visual observations of 25 male elephants ranging in age from 20 to 52 years to examine the influence of reproductive state and age on movement. We then used a three-state hidden Markov model (HMM) to detect musth behaviour in a subset of sequential tracking data. Our results demonstrate that male elephants increased their daily mean speed and range size with age and in musth. Furthermore, non-musth speed decreased with age, presumably reflecting a shift towards energy acquisition during non-musth. Thus, despite similar speeds and marginally larger ranges between reproductive states at age 20, by age 50, males were travelling 2.0 times faster in a 3.5 times larger area in musth relative to non-musth. The distinctiveness of musth periods over age 35 meant the three-state HMM could automatically detect musth movement with high sensitivity and specificity, but could not for the younger age class. We show that male elephants increased their energetic allocation into reproduction with age as the probability of reproductive success increases. Given that older male elephants tend to be both the target of legal trophy hunting and illegal poaching, man-made interference could drive fundamental changes in elephant reproductive tactics. Bio-logging, as our study reveals, has the potential both to quantify mature elephant reproductive tactics remotely and to be used to institute proactive management strategies around the reproductive behaviour of this charismatic keystone species.
- A mouse model of Proteus syndrome. [Journal Article]
- HMHum Mol Genet 2019 Jun 13
- Proteus syndrome is a mosaic, progressive overgrowth disorder caused by a somatic activating variant c.49G>A p.(E17K) in AKT1. The presentation in affected individuals is variable, with a diversity o…
Proteus syndrome is a mosaic, progressive overgrowth disorder caused by a somatic activating variant c.49G>A p.(E17K) in AKT1. The presentation in affected individuals is variable, with a diversity of tissues demonstrating abnormalities. Common manifestations include skin and bony overgrowth, vascular malformations, cysts, and benign tumors. We used two methods to create mouse models that had endogenously-regulated mosaic expression of the Proteus syndrome variant. Variant allele fractions (VAFs) ranged from 0-50% across numerous tissues in 44 Proteus syndrome mice. Mice were phenotypically heterogeneous with lesions rarely observed before 12 months of age. Vascular malformations were the most frequent finding with a total of 69 found in 29 of 44 Proteus syndrome mice. Twenty-eight cysts and ectasia, frequently biliary, were seen in 22 of 44 Proteus syndrome mice. Varying levels of mammary hyperplasia were seen in 10 of 16 female Proteus syndrome mice with other localized regions of hyperplasia and stromal expansion noted in several additional animals. Interestingly, 27 of 31 Proteus syndrome animals had non-zero blood VAF which is in contrast to the human disorder where it is rarely seen in peripheral blood. Identification of variant-positive cells by green fluorescent protein staining in chimeric Proteus syndrome mice showed that in some lesions, hyperplastic cells were predominantly GFP/Akt1E17K-positive and showed increased pAKT signal compared to GFP-negative cells. However, hyperplastic mammary epithelium was a mixture of GFP/Akt1E17K-positive and negative cells with some GFP/Akt1E17K-negative cells also having increased pAKT signal suggesting that the variant-positive cells can induce lesion formation in a non-cell autonomous manner.
- [Syndromes with vascular skin anomalies]. [Review]
- HHautarzt 2019; 70(7):474-480
- CONCLUSIONS: A diagnostic difficulty lies in the fact that not all syndromes associated with capillary nevi have been elucidated at the molecular level. For this reason, the preliminary dimension of the present review should be borne in mind. On the other hand, dermatologists in practice now have the fascinating chance to stimulate further advances in this particular field of knowledge by asking experts in dermatology, pediatrics or medical genetics how to solve the problem of molecular syndrome recognition in a puzzling case.
- First evidence of a therapeutic effect of miransertib in a teenager with Proteus syndrome and ovarian carcinoma. [Case Reports]
- AJAm J Med Genet A 2019; 179(7):1319-1324
- Proteus syndrome (PS) is an ultra-rare disease characterized by progressive, disproportionate, segmental overgrowth caused by a somatic gain-of-function mutation p.Glu17Lys in the oncogene AKT1. The …
Proteus syndrome (PS) is an ultra-rare disease characterized by progressive, disproportionate, segmental overgrowth caused by a somatic gain-of-function mutation p.Glu17Lys in the oncogene AKT1. The disease has high morbidity and mortality rates due to the increased risk for patients to develop cancer and progressive overgrowth. A teenage patient with severe PS phenotype developed a pelvic recurrence of low-grade serous ovarian carcinoma (LGSOC). Taking into consideration, recent results of the use of AKT inhibitors both in PS and AKT-mutant cancers, we treated the patient on a compassionate basis, with miransertib (ARQ 092), a potent, selective, allosteric AKT inhibitor. Targeted deep sequencing assay of PI3K/AKT pathway genes of the affected overgrowth lesion (cerebriform connective tissue nevus) and the tumor tissues detected the same activating AKT1 mutation in both. Treatment with miransertib led to a complete remission of the cancer and a significant improvement in the patients' everyday life. The treatment is still ongoing at 22 months. This is the first report showing the therapeutic effects of an AKT inhibitor on both benign and malignant tissues that harbor the same pathogenic AKT1 mutation. The present article showed that personalized medicine is feasible in ultra-rare diseases.
- Piriformis pyomyositis, a cause of piriformis syndrome-a systematic search and review. [Journal Article]
- CRClin Rheumatol 2019; 38(7):1811-1821
- Piriformis pyomyositis is a rare form of purulent skeletal myositis. As previous studies concerning piriformis pyomyositis had lower level of evidence and no systematic review has been published yet,…
Piriformis pyomyositis is a rare form of purulent skeletal myositis. As previous studies concerning piriformis pyomyositis had lower level of evidence and no systematic review has been published yet, we performed a systematic search to review and describe causes, symptoms, red flags, and available treatment options for piriformis pyomyositis. Using PubMed and PubMed Central databases, we found 21 articles describing 23 cases of piriformis pyomyositis. Based on the retrieved information, alongside acute sciatica like buttock and/or hip pain, high-grade fever, aggressive deep seated gluteal pain, neurological deficit of sciatic nerve distribution, positive straight leg raising test, and raised inflammatory biomarkers (erythrocyte sedimentation rate, ESR, C-reactive protein, CRP) provide clues for diagnosis of piriformis pyomyositis. Some cases were very ill but no death was documented. Staphylococcus aureus was the most common pathogen, but Group A as well as Group β Streptococcus, Salmonella typhi, Proteus mirabilis, Brucella melitensis, and Escherichia coli were also involved in the disorder. To treat the piriformis pyomyositis, broad-spectrum antibiotics were found to be useful; however, sometimes, antibiotic switching was warranted based on blood and tissue aspirate reports. Drainage and/or surgical exploration of the affected piriformis muscle were required in cases where antibiotics appeared ineffective. Piriformis pyomyositis is a rara avis and performing of prospective studies will hardly be feasible.
- Purple urine bag syndrome. [Journal Article]
- TNTidsskr Nor Laegeforen 2019 Mar 26; 139(6)
- Purple urine bag syndrome (PUBS) can occur in cases of bacteriuria with species expressing enzymes capable of converting tryptophan metabolites to red and blue pigments which are excreted in urine, l…
Purple urine bag syndrome (PUBS) can occur in cases of bacteriuria with species expressing enzymes capable of converting tryptophan metabolites to red and blue pigments which are excreted in urine, leaving a characteristic purple colour. Risk factors include urinary catheterisation, constipation and chronic kidney disease. Treatment includes catheter replacement, and antibiotics in case of urinary tract infection.
- Thrombectomy and reconstruction of the left vertebral artery after total arch replacement: never give up on postoperative stroke. [Journal Article]
- GTGen Thorac Cardiovasc Surg 2019 Mar 14
- The patient was a 64-year-old man who had aortic regurgitation, ischemic heart disease, a transverse aortic aneurysm, and an abdominal-common iliac aneurysm. Concomitant operations including aortic v…
The patient was a 64-year-old man who had aortic regurgitation, ischemic heart disease, a transverse aortic aneurysm, and an abdominal-common iliac aneurysm. Concomitant operations including aortic valve replacement, coronary artery bypass grafting, and total aortic arch replacement with elephant trunk technique were performed successfully. The patient developed postoperative cardiac tamponade on the 5th postoperative day, resulting in bulbar palsy due to occlusion of the dominant left vertebral artery. Thrombectomy of the vertebral artery with reconstruction by a saphenous vein was performed. The patient's neurological symptoms improved after the operation. Revascularization of ischemic stroke may yield neurological improvement even in patients after cardiovascular surgery.
- What's New in Genetic Skin Diseases. [Review]
- DCDermatol Clin 2019; 37(2):229-239
- The discoveries of new genes underlying genetic skin diseases have occurred at a rapid pace, supported by advances in DNA sequencing technologies. These discoveries have translated to an improved und…
The discoveries of new genes underlying genetic skin diseases have occurred at a rapid pace, supported by advances in DNA sequencing technologies. These discoveries have translated to an improved understanding of disease mechanisms at a molecular level and identified new therapeutic options based on molecular targets. This article highlights just a few of these recent discoveries for a diverse group of skin diseases, including tuberous sclerosis complex, ichthyoses, overgrowth syndromes, interferonopathies, and basal cell nevus syndrome, and how this has translated into novel targeted therapies and improved patient care.
New Search Next
- Congenital Limb Overgrowth Syndromes Associated with Vascular Anomalies. [Journal Article]
- RRadiographics 2019 Mar-Apr; 39(2):491-515
- Congenital limb length discrepancy disorders are frequently associated with a variety of vascular anomalies and have unique genetic and phenotypic features. Many of these syndromes have been linked t…
Congenital limb length discrepancy disorders are frequently associated with a variety of vascular anomalies and have unique genetic and phenotypic features. Many of these syndromes have been linked to sporadic somatic mosaicism involving mutations of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, which has an important role in tissue growth and angiogenesis. Radiologists who are aware of congenital limb length discrepancies can make specific diagnoses based on imaging findings. Although genetic confirmation is necessary for a definitive diagnosis, the radiologist serves as a central figure in the identification and treatment of these disorders. The clinical presentations, diagnostic and imaging workups, and treatment options available for patients with Klippel-Trenaunay syndrome, CLOVES (congenital lipomatous overgrowth, vascular anomalies, epidermal nevi, and scoliosis/spinal deformities) syndrome, fibroadipose vascular anomaly, phosphatase and tensin homolog mutation spectrum, Parkes-Weber syndrome, and Proteus syndrome are reviewed. ©RSNA, 2019.