A Rare Variant of Turner Syndrome (the X Isochromosome-X Syndrome): A Case Report

Background: Turner syndrome occurs in nearly one in every 2000-5000 female births. This syndrome is a genetic problem in the female phenotype and the most common sex chromosome anomaly. It is diagnosed based on clinical manifestations and cytogenetic examinations. The classic syndrome (i.e., monosomy X) makes up 50% of the cases while other forms contain X chromosome variants, which do not typically manifest as the classic X phenotype. Case Presentation: This study, presents a rare variant of Turner syndrome reported in a 20-year-old woman presenting with primary amenorrhea, hypothyroidism, and short stature who had hypergonadotropic hypogonadism with hypoplastic ovaries while without the clinical manifestations of the classic Turner syndrome. The karyotype was determined as X isochromosome-X syndrome [46 XXi (Xq)]. Conclusion: This rare syndrome occurs in approximately 7% of the cases of Turner syndrome. Rare variants of the syndrome should also be considered in female patients without the classic manifestations of Turner syndrome.

Subcutaneous extraskeletal osteosarcoma of the foot: A case report

Extraskeletal osteosarcoma (ESOS) is a rare variant of osteosarcoma which occurs exclusively in the soft tissue without any bone involvement. Subcutaneous ESOS, in particular, is very rare and is seen in <10% of cases. Here, we report a case of a subcutaneous tumor in the fourth web space of the left foot in a 73-year-old man. The diagnosis of ESOS was made on histology and by immunohistochemical reactivity to special AT-rich sequence-binding protein 2 (SATB2), which is a sensitive, nuclear marker of osteoblastic differentiation. We present this case because of its rarity and the use of SATB2 immunohistochemistry to confirm the diagnosis.

Granulomatous Slack Skin with Hypercalcemia Indolently Mimicking Sarcoidosis

<p class="abstract">Granulomatous slack skin is a rare variant of cutaneous T-cell lymphoma characterized by lax skin and granulomatous infiltrate with loss of elastic fibers on histology. We report a unique case of a female presenting with CD30-granulomatous slack skin complicated by hypercalcemia, initially diagnosed, and managed as sarcoidosis. Interestingly, she had a history of previously treated CD30+ cutaneous T-cell lymphoma. Granulomatous slack skin can frequently mimic other benign and malignant cutaneous diseases, prompting the need for clinical vigilance from dermatologists.</p>

rareSurvival: rare variant association analysis for time-to-event outcomes.

SRare variants have been proposed as contributing to the "missing heritability" of complex human traits. There has been much recent development of methodology to investigate association of complex traits with multiple rare variants within pre-defined "units" from sequence and array-based studies of the exome or genome. However, software for modelling time to event outcomes for rare variant associations has been under developed in comparison with binary and quantitative traits. We introduce a new command line application, rareSurvival, used for the analysis of rare variants with time to event outcomes. The program is compatible with high performance computing (HPC) clusters for batch processing. rareSurvival implements statistical methodology, which are a combination of widely used survival and gene-based analysis techniques such as the Cox proportional hazards model and the burden test. We introduce a novel piece of software that will be at the forefront of efforts to discover rare variants associated with a variety of complex diseases with survival endpoints. Availability & Implementation: rareSurvival is implemented in C#, available on Linux, Windows and Mac OS X operating systems. It is freely available (GNU General Public License, version 3) to download from https://www.liverpool.ac.uk/translational-medicine/research/statistical-genetics/software/. Download Mono for Linux or Mac OS X to run software.

Desmoplastic ameloblastoma in maxilla mimicking fibro-osseous leison: A case report

Desmoplastic Ameloblastoma accounts for 4% to 13% of all ameloblastomas and is a rare variant with high rate of recurrence. The desmoplastic variant of ameloblastoma usually appears in the anterior and premolar regions and sometimes resembles a benign fibro-osseous lesion showing a mixed radiolucent and radiopacity in the radiographic examination. Malignant transformation with repeated postsurgical recurrences have also been reported. In this paper we present a case of a 22-year-old female with swelling in the left upper jaw which turned out to be desmoplastic ameloblastoma. The pathologist and the clinician should be aware of the concepts and the association with malignant transformation and spread of the lesion in order to deliver appropriate treatment and to avoid further recurrences of the leison.

Extreme sampling for genetic rare variant association analysis of dichotomous traits with focus on infectious disease susceptibility

As genomic sequencing becomes more accurate and less costly, large cohorts and consortiums of cohorts are providing high power for rare variant association studies for many conditions. When large sample sizes are not attainable and the phenotype under study is continuous, an extreme phenotypes design can provide high statistical power with a small to moderate sample size. We extend the extreme phenotypes design to the dichotomous infectious disease outcome by sampling on extremes of the pathogenic exposure instead of sampling on extremes of phenotype. We use a likelihood ratio test (LRT) to test the significance of association between infection status and presence of susceptibility rare variants. More than 10 billion simulations are studied to assess the method. The method results in high sample enrichment for rare variants affecting susceptibility. Greater than 90% power to detect rare variant associations is attained in reasonable scenarios. The ordinary case-control design requires orders of magnitude more samples to achieve the same power. The Type I error rate of the LRT is accurate even for p-values < 10 -7 . We find that erroroneous exposure assessment can lead to power loss more severe than excluding the observations with errors. Nevertheless, careful sampling on exposure extremes can make a study feasible by providing adequate statistical power. Limitations of this method are not unique to this design, and the power is never less than that of the ordinary case-control design. The method applies without modification to other dichotomous outcomes that have strong association with a continuous covariate.