Cowden syndrome and Bannayan Riley Ruvalcaba syndrome represent one condition with variable expression and age-related penetrance: results of a clinical study of PTEN mutation carriers

BACKGROUND: The most commonly reported phenotypes described in patients with PTEN mutations are Bannayan-Riley-Ruvalcaba syndrome (BRRS), with childhood onset, macrocephaly, lipomas and developmental delay, and Cowden Syndrome (CS), an adult-onset condition recognised by mucocutaneous signs, with a risk of cancers, in particular those of the thyroid and breast. It has been suggested that BRRS and CS are the same condition, but the literature continues to separate them and seek a genotype-phenotype correlation. OBJECTIVE: To study the clinical features of patients with known PTEN mutations and observe any genotype-phenotype correlation. METHODS: In total, 42 people (25 probands and 17 non-probands) from 26 families of all ages with PTEN mutations were recruited through the UK clinical genetics services. A full clinical history and examination were undertaken. RESULTS: We were unable to demonstrate a genotype-phenotype correlation. Furthermore, our findings in a 31-year-old woman with CS and an exon 1 deletion refutes previous reports that whole exon deletions are only found in patients with a BRRS phenotype. CONCLUSION: Careful phenotyping gives further support for the suggestion that BRRS and CS are actually one condition, presenting variably at different ages, as in other tumour-suppressor disorders such as neurofibromatosis type 1. This has important counselling implications, such as advice about cancer surveillance, for children diagnosed with BRRS

Hereditary hyperferritinemia cataract syndrome: ocular, genetic, and biochemical findings

PURPOSE: To describe the cataract morphology and genetic and biochemical findings in a four-generation family with hereditary hyperferritinemia cataract syndrome (HHCS).METHODS: Family members of the proband with HHCS were investigated. DNA sequencing was carried out to identify the iron responsive element (IRE) of the L-ferritin gene in affected and non-affected family members. Molecular modeling allowed prediction of the structure of the mutant IRE in affected cases. Serum ferritin and transferrin saturation were determined using standard methods. All family members underwent slit lamp examination by an ophthalmologist to document presence of cataract or lens status. Cataract morphology was documented where present.RESULTS: This family with HHCS had the genetic heterozygous mutation G32C in the IRE of the L-ferritin mRNA. Lens opacities were detectable in young members of the family, and morphology of cataracts was consistent with previous reports. Biochemical testing demonstrated high serum ferritin levels in affected individuals.CONCLUSIONS: The morphology of cataracts in HHCS seems to be similar in all cases. In the heterozygous G32C mutation, the age at onset of cataracts is very early. Greater awareness of this condition among ophthalmologists will lead to effective family counseling of those affected, by genetic testing or simple biochemical tests. Serum ferritin levels can be effectively used to screen for this condition in suspected families

A comparison of clinical and dosimetric outcomes in patients receiving partial breast irradiation with photon-only versus mixed photon/electron treatment plans

PubMed ID: 21440433Several series evaluating external-beam partial breast irradiation (PBI) have linked negative cosmetic outcomes to large normal tissue treatment volumes. We compared patients treated with PBI whose treatment plans included only photons to those whose plans incorporated electrons. Twenty-seven patients were identified: median age 67 years, pT1 82%, pN0 56%, margin negative 100%. All received 38.5 Gy using 3-5 noncoplanar photon beams (6-15X). Electrons (9-20 MeV) were included in 59%. Median follow-up was 22 months. Ninety percent experienced good/excellent cosmetic outcomes. Two patients had fair cosmesis, and both were treated with a mixed photon/electron approach. Median conformity index for photon-only treatment plans was 1.7 (range, 0.9-2.0) and for photon/electron plans, 1.0 (0.3-1.4). Median percent ipsilateral breast volume receiving 100% and 50% of prescription dose was 19 and 50 for photon-only plans vs. 10 and 38 for photon/electron plans (p < 0.05). Median percent target volume receiving 100% and 95% of prescription dose was 93 and 98 for photon-only plans vs. 75 and 94 for photon/electron plans (p < 0.05). A mixed photon/electron, noncoplanar technique decreases the volume of treated normal breast tissue at the cost of slightly decreased tumor bed coverage. Further study is needed to determine whether this results in a more favorable therapeutic ratio than photon-only approaches. © 2011 American Association of Medical Dosimetrists

Spectral Characterization of Bennu Analogs Using PASCALE: A New Experimental Set-Up for Simulating the Near-Surface Conditions of Airless Bodies

We describe the capabilities, radiometric stability, and calibration of a custom vacuum environment chamber capable of simulating the near-surface conditions of airless bodies. Here we demonstrate the collection of spectral measurements of a suite of fine particulate asteroid analogs made using the Planetary Analogue Surface Chamber for Asteroid and Lunar Environments (PASCALE) under conditions like those found on Earth and on airless bodies. The sample suite includes anhydrous and hydrated physical mixtures, and chondritic meteorites (CM, CI, CV, CR, and L5) previously characterized under Earth- and asteroid-like conditions. And for the first time, we measure the terrestrial and extra-terrestrial mineral end members used in the olivine- and phyllosilicate-dominated physical mixtures under the same conditions as the mixtures and meteorites allowing us better understand how minerals combine spectrally when mixed intimately. Our measurements highlight the sensitivity of thermal infrared emissivity spectra to small amounts of low albedo materials and the composition of the sample materials. As the albedo of the sample decreases, we observe smaller differences between Earth- and asteroid-like spectra, which results from a reduced thermal gradient in the upper hundreds of microns in the sample. These spectral measurements can be compared to thermal infrared emissivity spectra of asteroid (101955) Bennu's surface in regions where similarly fine particulate materials may be observed to infer surface compositions. © 2020. The Authors.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Spectral Characterization of Bennu Analogs Using PASCALE: A New Experimental Set‐Up for Simulating the Near‐Surface Conditions of Airless Bodies

We describe the capabilities, radiometric stability, and calibration of a custom vacuum environment chamber capable of simulating the near-surface conditions of airless bodies. Here we demonstrate the collection of spectral measurements of a suite of fine particulate asteroid analogs made using the Planetary Analogue Surface Chamber for Asteroid and Lunar Environments (PASCALE) under conditions like those found on Earth and on airless bodies. The sample suite includes anhydrous and hydrated physical mixtures, and chondritic meteorites (CM, CI, CV, CR, and L5) previously characterized under Earth- and asteroid-like conditions. And for the first time, we measure the terrestrial and extra-terrestrial mineral end members used in the olivine- and phyllosilicate-dominated physical mixtures under the same conditions as the mixtures and meteorites allowing us better understand how minerals combine spectrally when mixed intimately. Our measurements highlight the sensitivity of thermal infrared emissivity spectra to small amounts of low albedo materials and the composition of the sample materials. As the albedo of the sample decreases, we observe smaller differences between Earth- and asteroid-like spectra, which results from a reduced thermal gradient in the upper hundreds of microns in the sample. These spectral measurements can be compared to thermal infrared emissivity spectra of asteroid (101955) Bennu's surface in regions where similarly fine particulate materials may be observed to infer surface compositions. © 2020. The Authors.Open access articleThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]