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Biomedical subjects

R E Stevenson

Publications and source records attributed to R E Stevenson.

At least 19 recordsLinked to original sources
PubMed2006

Golabi-Ito-Hall syndrome results from a missense mutation in the WW domain of the PQBP1 gene.

BACKGROUND: Golabi, Ito, and Hall reported a family with X linked mental retardation (XLMR), microcephaly, postnatal growth deficiency, and other anomalies, including atrial septal defect, in 1984. METHODS: This family was restudied as part of our ongoing study of XLMR, but significant linkage to X chromosome markers could not be found. Extreme short stature and microcephaly as well as other new clinical findings were observed. Mutations in the polyglutamine tract binding protein 1 gene (PQBP1) have recently been reported in four XLMR disorders (Renpenning, Hamel cerebro-palato-cardiac, Sutherland-Haan, and Porteous syndromes) as well as in several other families. The clinical similarity of our family to these patients with mutations in PQBP1, particularly the presence of microcephaly, short stature, and atrial septal defect, prompted examination of this gene. RESULTS: A missense mutation in PQBP1 was identified which changed the conserved tyrosine residue in the WW domain at position 65 to a cysteine (p.Y65C). CONCLUSIONS: This is the first missense mutation identified in PQBP1 and the first mutation in the WW domain of the gene. The WW domain has been shown to play an important role in the regulation of transcription by interacting with the PPxY motif found in transcription factors. The p.Y65C mutation may affect the proper functioning of the PQBP1 protein as a transcriptional co-activator.

Adolescent↗
PubMed2006

Disruption of DMD and deletion of ACSL4 causing developmental delay, hypotonia, and multiple congenital anomalies.

We have studied a male patient with significant developmental delay, growth failure, hypotonia, girdle weakness, microcephaly, and multiple congenital anomalies including atrial (ASD) and ventricular (VSD) septal defects. Detailed cytogenetic and molecular analyses revealed three de novo X chromosome aberrations and a karyotype 46,Y,der(X)inv(X) (p11.4q11.2)inv(X)(q11.2q21.32 approximately q22.2)del(X)(q22.3q22.3) was determined. The three X chromosome aberrations in the patient include: a pericentric inversion (inv 1) that disrupted the Duchenne muscular dystrophy (DMD) gene, dystrophin, at Xp11.4; an Xq11.2q21.32 approximately q22.2 paracentric inversion (inv 2) putatively affecting no genes; and an interstitial deletion at Xq22.3 that results in functional nullisomy of several known genes, including a gene previously associated with X-linked nonsyndromic mental retardation, acyl-CoA synthetase long chain family member 4 (ACSL4). These findings suggest that the disruption of DMD and the absence of ACSL4 in the patient are responsible for neuromuscular disease and cognitive impairment.

Abnormalities, Multiple↗
PubMed2005

Physiological and foliar symptom response in the crowns of Prunus serotina, Fraxinus americana and Acer rubrum canopy trees to ambient ozone under forest conditions.

The crowns of five canopy dominant black cherry (Prunus serotina Ehrh.), five white ash (Fraxinus americana L.), and six red maple (Acer rubrum L.) trees on naturally differing environmental conditions were accessed with scaffold towers within a mixed hardwood forest stand in central Pennsylvania. Ambient ozone concentrations, meteorological parameters, leaf gas exchange and leaf water potential were measured at the sites during the growing seasons of 1998 and 1999. Visible ozone-induced foliar injury was assessed on leaves within the upper and lower crown branches of each tree. Ambient ozone exposures were sufficient to induce typical symptoms on cherry (0-5% total affected leaf area, LAA), whereas foliar injury was not observed on ash or maple. There was a positive correlation between increasing cumulative ozone uptake (U) and increasing percent of LAA for cherry grown under drier site conditions. The lower crown leaves of cherry showed more severe foliar injury than the upper crown leaves. No significant differences in predawn leaf water potential (psi(L)) were detected for all three species indicating no differing soil moisture conditions across the sites. Significant variation in stomatal conductance for water vapor (g(wv)) was found among species, soil moisture, time of day and sample date. When comparing cumulative ozone uptake and decreased photosynthetic activity (P(n)), red maple was the only species to show higher gas exchange under mesic vs. drier soil conditions (P < 0.05). The inconsistent differences in gas exchange response within the same crowns of ash and the uncoupling relationship between g(wv) and P(n) demonstrate the strong influence of heterogeneous environmental conditions within forest canopies.

Acer↗
PubMed2004

Influence of light fleck and low light on foliar injury and physiological responses of two hybrid poplar clones to ozone.

Five-month old hybrid poplar clones NE388 and NE359 were exposed to square-wave 30, 55, and 80 ppb O(3) (8 h/day, 7 day/week) under constant high light (HL) and light fleck (LF) during 28 May-29 June 1999, and exposed to 30 and 55 ppb O(3) under HL, LF, and constant low light (LL) during 22 May-28 June 2000 within Continuously Stirred Tank Reactors (CSTR) in a greenhouse. Ramets of these two hybrid clones received similar total photosynthetically active radiation (PAR) within the LF and LL treatments. Visible foliar symptoms, leaf gas exchange, and growth were measured. More severe O(3) induced foliar symptoms were observed on ramets within the LF and LL treatments than within the HL treatment for both clones. The LF treatment resulted in significantly greater foliar injury than the LL treatment for NE388. The LF and LL treatments generally resulted in lower photosynthetic rates (Pn) for both clones, but did not affect stomatal conductance (g(wv)); therefore, the ratios of g(wv)/Pn and the O(3) uptake/Pn were greatest in plants grown under the LF treatment, followed by those grown under LL treatment; plants grown under HL had the lowest ratios of g(wv)/Pn and O(3) uptake/Pn. Greater ratios of g(wv)/Pn and O(3) uptake/Pn were consistently associated with more severe visible foliar symptoms. The negative impacts of the LF treatment on growth were greater than those of the LL treatment. Results indicate that not only the integral, but also the pattern of photo flux density, may affect carbon gain in plants. Increased foliar injury may be expected under light fleck conditions due to the limited repair capacity as a result of continuity of O(3) uptake while photosynthesis decreases under LL conditions.

Adaptation, Physiological↗
PubMed2004

Responses of hybrid poplar clones and red maple seedlings to ambient O(3) under differing light within a mixed hardwood forest.

The responses of ramets of hybrid poplar (Populus spp.) (HP) clones NE388 and NE359, and seedlings of red maple (Acer rubrum, L.) to ambient ozone (O(3)) were studied during May-September of 2000 and 2001 under natural forest conditions and differing natural sunlight exposures (sun, partial shade and full shade). Ambient O(3) concentrations at the study site reached hourly peaks of 109 and 98 ppb in 2000 and 2001, respectively. Monthly 12-h average O(3) concentrations ranged from 32.3 to 52.9 ppb. Weekly 12-h average photosynthetically active radiation (PAR) within the sun, partial shade and full shade plots ranged from 200 to 750, 50 to 180, and 25 to 75 micromol m(-2) s(-1), respectively. Ambient O(3) exposure induced visible foliar symptoms on HP NE388 and NE359 in both growing seasons, with more severe injury observed on NE388 than on NE359. Slight foliar symptoms were observed on red maple seedlings during the 2001 growing season. Percentage of total leaf area affected (%LAA) was positively correlated with cumulative O(3) exposures. More severe foliar injury was observed on plants grown within the full shade and partial shade plots than those observed on plants grown within the sun plot. Lower light availability within the partial shade and full shade plots significantly decreased net photosynthetic rate (Pn) and stomatal conductance (g(wv)). The reductions in Pn were greater than reductions in g(wv), which resulted in greater O(3) uptake per unit Pn in plants grown within the partial shade and full shade plots. Greater O(3) uptake per unit Pn was consistently associated with more severe visible foliar injury in all species and/or clones regardless of differences in shade tolerance. These studies suggest that plant physiological responses to O(3) exposure are likely complicated due to multiple factors under natural forest conditions.

Acer↗
PubMed2003

A multi-variate statistical model integrating passive sampler and meteorology data to predict the frequency distributions of hourly ambient ozone (O3) concentrations.

A multi-variate, non-linear statistical model is described to simulate passive O3 sampler data to mimic the hourly frequency distributions of continuous measurements using climatologic O3 indicators and passive sampler measurements. The main meteorological parameters identified by the model were, air temperature, relative humidity, solar radiation and wind speed, although other parameters were also considered. Together, air temperature, relative humidity and passive sampler data by themselves could explain 62.5-67.5% (R(2)) of the corresponding variability of the continuously measured O3 data. The final correlation coefficients (r) between the predicted hourly O3 concentrations from the passive sampler data and the true, continuous measurements were 0.819-0.854, with an accuracy of 92-94% for the predictive capability. With the addition of soil moisture data, the model can lead to the first order approximation of atmospheric O3 flux and plant stomatal uptake. Additionally, if such data are coupled to multi-point plant response measurements, meaningful cause-effect relationships can be derived in the future.

Air Pollutants↗
PubMed2003

Physiological and foliar injury responses of Prunus serotina, Fraxinus americana, and Acer rubrum seedlings to varying soil moisture and ozone.

Sixteen black cherry (Prunus serotina, Ehrh.), 10 white ash (Fraxinus americana, L.) and 10 red maple (Acer rubrum, L.) 1-year old seedlings were planted per plot in 1997 on a former nursery bed within 12 open-top chambers and six open plots. Seedlings were exposed to three different ozone scenarios (ambient air: 100% O3; non-filtered air: 98% ambient O3; charcoal-filtered air: 50% ambient O3) within each of two different water regimes (nine plots irrigated, nine plots non-irrigated) during three growing seasons. During the 1998 and 1999 growing season, leaf gas exchange, plant water relations, and foliar injury were measured. Climatic data,ambient- and chamber-ozone-concentrations were monitored. We found that seedlings grown under irrigated conditions had similar (in 1998) but significantly higher gas exchange rates (in 1999) than seedlings grown within non-irrigated plots among similar ozone exposures. Cherry and ash had similar ozone uptake but cherry developed more ozone-induced injury (< 34% affected leaf area, LAA) than ash (<5% LAA), while maple rarely showed foliar injury, indicating the species differed in ozone sensitivity. Significantly more severe injury on seedlings grown under irrigated conditions than seedlings grown under non-irrigated conditions demonstrated that soil moisture altered seedling responses to ambient ozone exposures.

Acer↗
PubMed2003

Use of bioindicators and passive sampling devices to evaluate ambient ozone concentrations in north central Pennsylvania.

Ambient concentrations of tropospheric ozone and ozone-induced injury to black cherry (Prunus serotina) and common milkweed (Asclepias syriaca) were determined in north central Pennsylvania from 29 May to 5 September 2000 and from 28 May to 18 September 2001. Ogawa passive ozone samplers were utilized within openings at 15 forested sites of which six were co-located with TECO model 49 continuous ozone monitors. A significant positive correlation was observed between the Ogawa passive samplers and the TECO model 49 continuous ozone monitors for the 2000 (r=0.959) and 2001 (r=0.979) seasons. In addition, a significant positive correlation existed in 2000 and 2001 between ozone concentration and elevation (r=0.720) and (r=0.802), respectively. Classic ozone-induced symptoms were observed on black cherry and common milkweed. In 2000, initial injury was observed in early June, whereas for the 2001 season, initial injury was initially observed in late June. During both seasons, injury was noted at most sites by mid- to late-July. Soil moisture potential was measured for the 2001 season and a significant positive relationship (P<0.001) showed that injury to black cherry was a function of cumulative ozone concentrations and available soil moisture.

Air Pollutants↗
PubMed2002

Non-syndromic X-linked mental retardation associated with a missense mutation (P312L) in the FGD1 gene.

Three brothers with non-syndromal X-linked mental retardation were found to have a novel missense mutation in FGD1, the gene associated with the Aarskog syndrome. Although the brothers have short stature and small feet, they lack distinct craniofacial, skeletal or genital findings suggestive of Aarskog syndrome. Their mother, the only obligate carrier available for testing, has the FGD1 mutation. The mutation, a C934T base change in exon 4, results in the proline at position 312 to be substituted with a leucine. This missense mutation is predicted to eliminate a beta-turn, creating an extra-long stretch of coiled sequence which may affect the orientations of an SH3 (Src homology 3) binding domain and the first structural conserved region. A new molecular defect associated with non-syndromal X-linked mental retardation affords an opportunity to seek specific diagnosis in males with previously unexplained developmental delays and this opens further predictive tests in families at risk.

Adult↗
PubMed2002

Cognitive function in Coffin-Lowry syndrome.

Coffin-Lowry syndrome (CLS) is an X-linked disorder associated with mental retardation, distinctive facies and hands, hypotonia, and skeletal abnormalities. The syndrome results from mutations in the RSK2 gene located in Xp22.2. Although the syndrome has been elucidated clinically, few, if any, studies have focused on the cognitive deficits of the affected males or carrier females. The subjects of the present study were selected from two African-American families who have the same missense mutation (C340T) in RSK2. The subjects included six affected males, seven carrier females, three normal males and three non-carrier (normal) females. Normal family members served as contrast/comparison cohorts to control for socio-economic, sociocultural and genetic variables which would impinge on intellectual abilities. Analysis of cognitive function, as measured by the Stanford-Binet Intelligence Scale, 4th edn, demonstrated a distinct hierarchy of abilities from normal to carrier to affected patients. The mean composite IQs of the cohorts were 90.8, 65.0 and 43.2 for normal, carrier and affected individuals, respectively. These findings lend support to the clinical concept of negative intellectual effects in carriers of certain X-linked mental retardation conditions. X-inactivation studies showed that carrier females had mild to significant skewing. Normal females in the family did not demonstrate skewing. The correlation coefficient between IQ and X-inactivation status among carriers was not significant.

Black or African American↗
PubMed2002

Clinical and molecular contributions to the understanding of X-linked mental retardation.

X-linked mental retardation (XLMR) was first recognized in the 1940s, long before any human genes had been mapped. It is now estimated that XLMR has a prevalence of 2.6 cases per 1,000 population, accounting for over 10% of all cases of mental retardation. It is likely that over 150 genes are associated with XLMR. Fragile X syndrome, the most common form of XLMR, has a prevalence of about 1 in 4,000 males. Clinically, XLMR exists in syndromic (mental retardation with other somatic, neurological, behavioral, or metabolic findings) and nonsyndromic (mental retardation without other distinguishing features) forms. However, recent findings have caused this distinction to become blurred as mutations in some genes have been found in both syndromic and nonsyndromic XLMR. Progress in XLMR gene identification has allowed some insight into various pathways and cellular activities involved in developing cognitive functions. The genes involve signaling pathways, transcription factors, cytoskeletal organization, cell adhesion and migration, and maintenance of the cell membrane potential.

Chromosome Mapping↗
PubMed2001

Split hand/split foot malformation with hearing loss: first report of families linked to the SHFM1 locus in 7q21.

Developmental anomalies of the appendicular skeleton are among the most common and easily ascertained birth defects. Split hand/split foot malformations, distinctive in having deficiency of the central rays, occur as isolated anomalies and as one component of multisystem syndromes. The clinical and molecular characterization of a new syndrome, found in two unrelated families, consisting of split foot with hearing loss, is presented here. As in other split hand/split foot conditions, variable expression and reduced penetrance is notable. In the larger family, variably expressed split foot malformations were found in 6 of 11 gene carriers. and mild-to-moderate sensorineural hearing loss in 4. Split hand and cleft lip/palate in one individual and tibial deficiency in another suggest that these malformations are uncommon components of the syndrome. Ectodermal abnormalities did not occur. In the second family, variable split foot was observed in 3 of 4 gene carriers, and sensorineural deafness was present in 3. Split hand was only seen in a gene carrier who also had split foot and deafness. One gene carrier only had deafness. The gene for split hand split foot with sensorineural hearing loss was linked to markers in 7q21 in both families, with a combined (maximum LOD score of 4.37 at theta = 0.0 for locus D7S527) at 80% penetrance. Efforts to identify the responsible gene have not yet been successful.

Abnormalities, Multiple↗
PubMed2000

Spectrum of Schwartz-Jampel syndrome includes micromelic chondrodysplasia, kyphomelic dysplasia, and Burton disease.

Follow-up and re-evaluation of four patients originally described as examples of severe infantile "micromelic chondrodysplasia" resembling Kniest disease, "kyphomelic dysplasia," and "Burton skeletal dysplasia" revealed the diagnosis of Schwartz-Jampel syndrome (SJS, myotonic chondrodysplasia) in all of them. SJS may be suspected in neonates with Kniest-like chondrodysplasia, congenital bowing of shortened femora and tibiae, and facial manifestations consisting of a small mouth, micrognathia, and possibly pursed lips. The disorder must be differentiated from the Stüve-Wiedemann syndrome, a genetically distinct myotonic chondrodysplasia with similar clinical but different skeletal changes and an unfavorable early prognosis. The demise of "kyphomelic dysplasia" as a nosological entity reemphasizes the symptomatic nature of congenital bowing of the long bones.

Abnormalities, Multiple↗
PubMed2000

Splitting and lumping in the nosology of XLMR.

Although it is assumed that genes that influence cognitive function are ubiquitous in the human genome, to date, more such genes have been found on the X chromosome than on any other comparable segment of the autosomes. This is in large measure because of the power of hemizygosity in exposing mutations of X-linked genes in males. Clinical manifestations, mapping of gene loci by linkage analysis or chromosome rearrangements, and gene identification by positional cloning or mutational analysis of candidate genes have permitted extensive lumping and splitting within the large and heterogeneous category of X-linked mental retardation (XLMR). Approximately 130 XLMR syndromes have been identified, 25 gene loci have been mapped and cloned, and 55 other loci have been mapped but not cloned. Well-recognized syndromes (e.g., Fragile X and Coffin-Lowry syndromes) and syndromes represented by only a single family (e.g., Arena and monoamine oxidase-A syndromes) are among these more or less well-defined entities. In addition, more than 75 families with nonsyndromal XLMR have been regionally mapped and 7 causative genes have been identified.

Abnormalities, Multiple↗