Divisions of Human Genetics

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Divisions of Human Genetics

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Sheil A.,Divisions of Pathology and Laboratory Medicine | Knapke S.,Divisions of Human Genetics | Geller J.I.,University of Cincinnati
Journal of Pediatric Hematology/Oncology | Year: 2016

The proportion and clinical characteristics of Gardner fibromas (GAFs) that are sporadic versus familial adenomatous polyposis (FAP)-associated have not been clearly established. We report on 7 patients diagnosed with GAF who underwent APC sequencing and duplication/deletion testing. Three (43%) were found to have underlying APC germline perturbations consistent with FAP; these patients had multifocal (1) or large; unresectable (2) GAFs. The 4 patients with negative APC testing each had a single resectable GAF. β-catenin reactivity was noted in all FAPassociated GAFs and in 1/4 APC wild-type cases. FAP-associated GAFs may be less common than sporadic GAFs and can demonstrate clinically distinct features. © 2016 Wolters Kluwer Health, Inc. All rights reserved.


PubMed | University of Pennsylvania, Children's Hospital of Philadelphia and Divisions of Human Genetics.
Type: Journal Article | Journal: Pediatrics | Year: 2016

Pseudotumor cerebri syndrome (PTCS) is characterized by increased intracranial pressure with normal brain parenchyma and cerebrospinal fluid constituents. PTCS after withdrawal of systemic corticosteroids also has been described in children. In contrast, to our knowledge, PTCS after withdrawal of inhaled glucocorticoids has not previously been described. Here we report the case of an 8-year and 6-month-old girl who developed signs and symptoms consistent with PTCS after withdrawal of inhaled glucocorticoids. The patient had excellent adherence to inhaled glucocorticoid therapy for 1 year before presentation, after which the therapy was stopped for concern related to poor growth. The withdrawal of inhaled glucocorticoids was associated with the development of severe headaches and diplopia, and further clinical examination led to the patients diagnosis of likely PTCS. Although its occurrence is likely rare, clinicians caring for the many children receiving inhaled glucocorticoid therapy should be aware of the potential for PTCS after abrupt withdrawal of such treatment, and consider ophthalmology evaluation if patients report suggestive symptoms, such as headaches or vision changes in this context.


Wang S.,Chinese PLA General Hospital | Li R.,Divisions of Human Genetics | Fettermann A.,Medical University of Vienna | Li Z.,Chinese PLA General Hospital | And 13 more authors.
Circulation Research | Year: 2011

RATIONAL:: Despite maternal transmission of hypertension in some pedigrees, pathophysiology of maternally inherited hypertension remains poorly understood. Objective: To establish a causative link between mitochondrial dysfunction and essential hypertension. METHOD AND RESULTS:: A total of 106 subjects from a large Chinese family underwent clinical, genetic, molecular, and biochemical evaluations. Fifteen of 24 adult matrilineal relatives exhibited a wide range of severity in essential hypertension, whereas none of the offspring of affected fathers had hypertension. The age at onset of hypertension in the maternal kindred varied from 20 years to 69 years, with an average of 44 years. Mutational analysis of their mitochondrial genomes identified a novel homoplasmic 4263A>G mutation located at the processing site for the tRNA 5′-end precursor. An in vitro processing analysis showed that the 4263A>G mutation reduced the efficiency of the tRNA precursor 5′-end cleavage catalyzed by RNase P. tRNA Northern analysis revealed that the 4263A>G mutation caused â46% reduction in the steady-state level of tRNA. An in vivo protein-labeling analysis showed 32% reduction in the rate of mitochondrial translation in cells carrying the 4263A>G mutation. Impaired mitochondrial translation is apparently a primary contributor to the reductions in the rate of overall respiratory capacity, malate/glutamate-promoted respiration, succinate/glycerol-3-phosphate-promoted respiration, or N,N,N′,N′-tetramethyl-p-phenylenediamine/ascorbate-promoted respiration and the increasing level of reactive oxygen species in cells carrying the 4263A>G mutation. Conclusions: These data provide direct evidence that mitochondrial dysfunction caused by mitochondrial tRNA 4263A>G mutation is involved in essential hypertension. Our findings may provide new insights into pathophysiology of maternally transmitted hypertension. © 2011 American Heart Association, Inc.

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