A renal cell carcinoma with EWSR1‐TFE3 fusion gene

Both EWSR1 and TFE3 are well‐known oncogenes. EWSR1 encodes an RNA‐binding protein involved in multiple soft tissue tumors, including Ewing's sarcoma/peripheral neuroectodermal tumor, desmoplastic small round cell tumor, soft tissue clear cell sarcoma (malignant melanoma of soft parts), extraskeletal myxoid chondrosarcoma, and myxoid liposarcomas. TFE3 regulates both Golgi and lysosomal homeostasis and is rearranged in renal cell carcinoma (RCC), alveolar soft part sarcoma, epithelioid hemangioendothelioma, and perivascular epitheloid cell tumors (PEComas). In this report, we found a rare case of RCC with a fusion between 5′ EWSR1 and 3′ TFE3. The fusion product retained most functional motifs of TFE3. The oncogenic mechanism likely involves TFE3 overexpression through its juxtaposition with the regulatory elements of EWSR1 and its translocation to the nucleus, resulting in the deregulation of Golgi and lysosomal homeostasis. This is a second case of RCC containing EWSR1‐TFE3 fusion.     

A novel RBMX‐TFE3 gene fusion in a highly aggressive pediatric renal perivascular epithelioid cell tumor

We report an Xp11 translocation perivascular epithelioid cell tumor (PEComa) with a novel RBMX‐TFE3 gene fusion, resulting from a paracentric X chromosome inversion, inv(X)(p11;q26). The neoplasm occurred in an otherwise healthy 12‐year‐old boy who presented with a large left renal mass with extension into the inferior vena cava. The patient was found to have multiple pulmonary metastases at diagnosis and died of disease 3 months later. The morphology (epithelioid clear cells with alveolar and nested architecture) and immunophenotype (TFE3 and HMB45 strongly positive; actin, desmin, and PAX8 negative) was typical of an Xp11 translocation PEComa; however, TFE3 rearrangement was initially not detected by routine TFE3 break‐apart fluorescence in situ hybridization (FISH). Further RNA sequencing revealed a novel RBMX‐TFE3 gene fusion, which was subsequently confirmed by fusion assay FISH, using custom design RBMX and TFE3 come‐together probes. This report describes a novel TFE3 gene fusion partner, RBMX, in a pediatric renal PEComa patient associated with a fulminant clinical course. As documented in other intrachromosomal Xp11.2 inversions, such as fusions with NONO, RBM10, or GRIPAP1 genes, the TFE3 break‐apart might be below the FISH resolution, resulting in a false negative result.     

Maturity‐related differences in physical activity among 10‐ to 12‐year‐old girls

Besides environmental and psycho‐social factors explaining the variation in physical activity levels during adolescence, some evidence suggests that biological processes are involved in regulating habitual daily physical activity and energy expenditure. The purpose of this study was to examine the influence of biological maturity status on physical activity. Chronological age, standing height, sitting height, and body mass were measured cross‐sectionally in 268 girls, aged 9.5 to 11.5 years. Biological maturity groups (Early, Average, Late) were created according to estimated age at peak‐height‐velocity (estAPHV). Habitual physical activity was determined with a pedometer (Yamax Digiwalker SW‐200) over a 7‐day period. Differences in steps/day across maturity groups were examined by ANCOVA, controlling separately for time the pedometer was worn, leg length, and body mass. Mean pedometer steps/day was 10,822 ± 2,639. As expected, body size varied by maturity status (e.g., early > average > late). Significant maturity group differences were found with early maturing girls showing lower activity levels compared to average or late maturers. These differences remained after controlling for time the pedometer was worn and leg length; however, the differences were no longer significant when controlling for body mass. The results suggest that biological maturity status influences physical activity levels in girls between 10 and 12 years of age but the relationship is not independent of body mass. Further research is needed to establish the complex inter‐relationships among adiposity, biological maturation, and energy expenditure during puberty. Am. J. Hum. Biol., 2010. © 2009 Wiley‐Liss, Inc.     

A novel low‐grade nasopharyngeal adenocarcinoma characterized by a GOLGB1‐BRAF fusion gene

Nasopharyngeal adenocarcinoma is a rare malignancy that is classified into conventional/surface‐ and salivary‐types. Herein we report the case of a 52‐year‐old male who presented with a right nasopharyngeal mass and right‐sided hearing loss. Diagnostic imaging revealed a circumscribed 1.7 cm mass centred in the right antero‐lateral aspect of the nasopharynx. A biopsy showed a gland‐forming neoplasm that was in continuity with the surface epithelium. The tumor exhibited a nested to micro‐papillary architecture, with mild cytologic atypia. Immunohistochemistry demonstrated diffuse staining for CK7, SOX10, and p16; the abluminal layer was highlighted by CK5 and p63, while the luminal cells expressed CD117. The tumor was not amenable to subclassification and was diagnosed as a low‐grade nasopharyngeal adenocarcinoma, not otherwise specified (NOS). Subsequent RNA sequencing was performed which identified a novel GOLGB1‐BRAF fusion product. Based on its unique morphology and molecular findings, this is presumed to represent a novel subtype of nasopharyngeal adenocarcinoma. In addition to being of diagnostic relevance, this fusion may ultimately represent a potential therapeutic target.     

To have and to hold: Episodic memory in 3‐ and 4‐year‐old children

Episodic memory endows us with the ability to reflect on our past and plan for our future. Most theorists argue that episodic memory emerges during the preschool period and that its emergence might herald the end of childhood amnesia. Here, we show that both 3‐ and 4‐year‐old children form episodic memories, but that 3‐year‐old children fail to retain those memories following a delay (Experiments 1 and 2). In contrast, 4‐year‐old children retained episodic memories over delays of 24 hr (Experiment 1) and 1 week (Experiment 3). This marked change in the retention of episodic memories between 3 and 4 years of age suggests that it is our ability to retain, rather than to form, an episodic memory that limits our ability to recall episodes from early childhood. © 2011 Wiley Periodicals, Inc. Dev Psychobiol 55: 125–132, 2013     

TCF12 microdeletion in a 72‐year‐old woman with intellectual disability

Heterozygous mutations in TCF12 were recently identified as an important cause of craniosynostosis. In the original series, 14% of patients with a mutation in TCF12 had significant developmental delay or learning disability. We report on the first case of TCF12 microdeletion, detected by array‐comparative genomic hybridization, in a 72‐year‐old patient presenting with intellectual deficiency and dysmorphism. Multiplex ligation‐dependent probe amplification analysis indicated that exon 19, encoding the functionally important basic helix‐loop‐helix domain, was included in the deleted segment in addition to exon 20. We postulate that the TCF12 microdeletion is responsible for this patient's intellectual deficiency and facial phenotype. © 2015 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc.     

The prevalence of lip vermilion morphological traits in a 15‐year‐old population

The aim of this study is to describe and categorize the various lip vermilion morphological traits, prevalence, and associations present in a 15‐year‐old population The instrument we developed was checked for the reliability of assessment. The study is a cross‐sectional study of lip vermilion morphology in 2,246 fifteen‐year‐old children. Three‐dimensional surface laser scans were taken of the children, and a classification scale was derived and assessed for intra‐ and inter‐reliability. The prevalence of lip vermilion morphological traits and associations was identified. Certain features are found to be likely to be associated with each other: thin philtrum and smooth/deep indentation of the philtrum; wide philtrum and smooth/normal gradient, flat/absent Cupid's bow and smooth/normal/indentation near nose, V‐shaped Cupid's bow and indentation in middle/deep groove; thin upper lip vermilion and deep groove; thick upper lip vermilion and smooth philtrum; acute nasolabial angle and upper lip double border and thick upper lip vermilion; obtuse nasolabial angle and thin upper lip vermilion. In conclusion, we present a new method to identify the various morphological features of the vermilion of the lips. The prevalence of morphological traits has been identified in this 15‐year‐old population. In addition, the association of lip traits has been reported. This classification scale may be utilized to ascertain prevalence of features amongst other ethnic groups, to gain knowledge of what is considered to be attractive features, and to determine genotype/phenotype associations. © 2012 Wiley Periodicals, Inc.