PubMed Health⌕ Search

Biomedical subjects

M G Butler

Publications and source records attributed to M G Butler.

At least 19 recordsLinked to original sources
PubMed2006

Circulating adiponectin levels, body composition and obesity-related variables in Prader-Willi syndrome: comparison with obese subjects.

BACKGROUND: People with obesity and/or the metabolic syndrome have an increased risk for developing diabetes and cardiovascular disease and may have low adiponectin levels. The obesity associated with Prader-Willi syndrome (PWS) would be expected to have similar complications. However, it was recently reported that, despite their adiposity, people with PWS have reduced visceral fat and are less likely to develop diabetes mellitus or the metabolic syndrome compared with people with simple obesity. OBJECTIVE: To determine if plasma adiponectin levels and other variables relevant to diabetes and cardiovascular risk are different in a cohort of PWS subjects with known genetic subtypes compared with age-, sex- and weight-matched control subjects. RESULTS: Fasting plasma glucose, C-peptide, triglycerides, leptin and cholesterol levels were similar in PWS and obese subjects. Our 20 PWS subjects (mean age = 27.7 years) had higher percent body fat (54.1 vs 48.5%) determined by DEXA measurements and lower percent lean mass (45.9 vs 51.5%) compared with 14 obese controls (mean age = 26.9 year). Plasma adiponectin levels were significantly higher in PWS (15.5 +/- 8.2 microg/ml) than in obese controls (7.5 +/- 2.7 microg/ml). A significant positive correlation was found with insulin sensitivity in PWS subjects (r = 0.75, P = 0.0003) but not in obese controls (r = 0.36, P = 0.20). DISCUSSION: Our study confirmed an earlier observation of higher adiponectin levels in PWS subjects and less insulin resistance proportionate to their obesity status than found in subjects with simple obesity. Furthermore, no differences were seen in PWS subjects with the chromosome 15 deletion or maternal disomy 15. The reported excessive visceral adiposity in subjects with simple obesity compared with PWS may be associated with decreased production and lower circulating levels of adiponectin.

Adiponectin↗
PubMed2006

A measure of food seeking in individuals with Prader-Willi syndrome.

BACKGROUND: Individuals with Prader-Willi syndrome (PWS), a chromosome 15 genetic disorder, often have a significant preoccupation with food and problem behaviour related to food seeking is often prevalent. METHODS: In the present study, we compared how individuals with PWS responded on a survey regarding the acceptability of food in various locations that varied according to degree of appropriateness for human consumption (e.g. food on a plate, food in a garbage can). For a subgroup of participants, we observed how they actually responded when placed in a room with food items placed in the same locations depicted in the survey. In the first part of the study, three groups (25 typically developing individuals, 7 individuals with intellectual disability (ID), and 19 individuals with PWS) responded to a visual survey to determine the degree of acceptability of food items in various locations (e.g. on a table near a hairbrush, on the floor behind a toy box, in a trash can). In the second part of the study, these food items (popcorn, jelly beans) were placed in the 12 locations described above. Nine individuals diagnosed with PWS (deletion type) and three individuals with ID were given some break time in the room for 15 min. The amount of food consumed, the time spent food seeking, and time spent interacting with materials were measured. RESULTS: Results of the survey indicated that the PWS group differed significantly with regard to how they responded on the survey from the typically developing group, but did not differ significantly from the ID group. Results of the food seeking observations indicated that only three individuals with PWS ate a significant number of items. The three individuals did not differ from the rest of the group according to IQ or compulsivity score; however, they had significantly lower body mass index (BMI) scores and were younger than the other participants. CONCLUSIONS: The findings from the survey indicate that individuals with PWS are able to discriminate the appropriateness of eating items in more or less contaminated areas; however, the amount of time spent seeking food and the amount of food covertly consumed appeared to depend more directly on age and BMI.

Adolescent↗
PubMed2006

Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism.

OBJECTIVE: To screen cDNA for NLGN3 and NLGN4 from lymphoblastoid cells from autistic subjects. METHODS AND RESULTS: 10 young autistic females and 30 non-autistic subjects were studied for alterations in two X linked genes, NLGN3 and NLGN4. A novel NLGN4 isoform lacking exon 4, which occurred de novo on the paternal allele, was identified in one of the autistic females. Monoallelic expression of NLGN4 was seen in this subject and in 11 of 14 informative autistic and non-autistic females using a single nucleotide polymorphism found at 3' UTR. Additionally, the NLGN3 transcript was present in two isoforms (with and without exon 7) in nine of 10 autistic females and in 30 non-autistic subjects, including parents of the autistic female having only the complete transcript with exon 7, and from the whole brain of a control. The novel truncated NLGN3 product may have a regulatory role, as reported in other proteins (for example, vasopressin receptor) by attenuating the function of the full length isoform, resulting in a reduction of the mature protein. Three dimensional protein structures were characterised using comparative modelling, and significant changes were suggested in the protein cores for these two neuroligin isoforms. CONCLUSIONS: Splice variants may lead to potentially abnormal neuroligins in the causation of autism spectrum disorders.

Alleles↗
PubMed2005

Brief report: non-random X chromosome inactivation in females with autism.

Autism is a heterogeneous neurodevelopmental disorder with a 3-4 times higher sex ratio in males than females. X chromosome genes may contribute to this higher sex ratio through unusual skewing of X chromosome inactivation. We studied X chromosome skewness in 30 females with classical autism and 35 similarly aged unaffected female siblings as controls using the polymorphic androgen receptor (AR) gene. Significantly, increased X chromosome skewness (e.g., >80:20%) was detected in our autism group (33%) compared to unaffected females (11%). X chromosome skewness was also seen in 50% of the mothers with autistic daughters. No mutation was seen in the promoter region of the XIST gene reported to be involved in X chromosome inactivation in our subjects. X chromosome skewness has been reported in female carriers of other neurological disorders such as X-linked mental retardation, adrenoleukodystrophy and Rett syndrome.

Autistic Disorder↗
PubMed2005

Insulin resistance and obesity-related factors in Prader-Willi syndrome: comparison with obese subjects.

Prader-Willi syndrome (PWS), the most common genetic cause of marked obesity in humans, is usually due to a de novo paternally derived chromosome 15q11-q13 deletion or maternal disomy 15 [(uniparental disomy (UPD)]. Obesity is due to energy imbalance, but few studies have examined fat patterning and obesity-related factors in subjects with PWS (deletions and UPD) compared with subjects with simple obesity. We examined for differences in fatness patterning and lipid, leptin, and glucose and insulin levels in subjects with simple obesity and PWS and adjusted for gender, age, and body mass index (BMI). Fasting peripheral blood samples and cross-sectional magnetic resonance image scans at the level of the umbilicus were obtained in 55 subjects ranging in age from 10.4 to 49 years: 20 PWS deletion, 17 PWS UPD, and 18 obese controls. Subcutaneous fat area (SFA) and intra-abdominal visceral fat area (VFA) were calculated. No significant difference was seen between the PWS deletion subjects or PWS UPD subjects for fatness measurements or leptin levels. Twenty-three of 37 PWS subjects met the criteria for obesity (BMI > 95th percentile). No significant differences were observed for SFA and VFA between the PWS subjects judged to be obese and control subjects with simple obesity. There was an overall trend for decreased VFA in the PWS subjects but not significantly different. VFA was significantly positively correlated with both fasting insulin and total cholesterol in PWS deletion subjects but not in PWS UPD subjects or obese controls. Fasting insulin level was significantly lower in the obese PWS subjects compared with subjects with simple obesity, and insulin sensitivity (QUICKI) was significantly higher in PWS subjects with obesity. Homeostasis model assessment (HOMA) and QUICKI values were correlated and in opposite directions with triglycerides in the obese PWS subjects but not in the obese controls. Subjects in each group were stratified according to published criteria on the basis of their level of visceral fat (e.g. > or = 130 cm(2)) to assess the influence of VFA on metabolic abnormalities. In the obese PWS subjects, the fasting triglyceride, glucose, and insulin levels, and HOMA value were significantly elevated, while the QUICKI value was significantly lower in those with VFA > or = 130 cm(2). Such significant differences were not seen in the obese control group. Our results indicate that VFA may be regulated differently in PWS subjects compared to individuals with simple obesity. Insulin resistance is lower in PWS subjects and insulin sensitivity is higher compared with obese controls. PWS subjects with increased VFA may be at a higher risk of obesity-related complications compared to PWS subjects without increased VFA.

Adipose Tissue↗
PubMed2005

Subset of individuals with autism spectrum disorders and extreme macrocephaly associated with germline PTEN tumour suppressor gene mutations.

The genetic aetiology of autism remains elusive. Occasionally, individuals with Cowden syndrome (a cancer syndrome) and other related hamartoma disorders such as Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-like conditions, are characterised by germline PTEN mutations, and may have neurobehavioural features resembling autism as well as overgrowth and macrocephaly. Therefore, we undertook PTEN gene mutation analysis in 18 subjects mainly prospectively ascertained with autism spectrum disorder and macrocephaly. Of these 18 autistic subjects (13 males and five females; ages 3.1-18.4 years) with a head circumference range from 2.5 to 8.0 standard deviations above the mean, three males (17%) carried germline PTEN mutations. These three probands had previously undescribed PTEN mutations: H93R (exon 4), D252G (exon 7), and F241S (exon 7). They had the larger head circumference measurements amongst all our study subjects. The three residues altered in our patients were highly evolutionarily conserved. We suggest that PTEN gene testing be considered for patients with autistic behaviour and extreme macrocephaly. The gene findings may impact on recurrence risks as well as medical management for the patient.

Adolescent↗
PubMed2003

Five new subjects with ring chromosome 22.

Ring chromosome 22, a rare cytogenetic finding, was first described by Weleber et al. in 1968. Since then approximately 50 patients have been reported in the medical literature. We describe five previously unreported subjects with ring chromosome 22 syndrome, summarize the clinical findings of reported patients from the literature and discuss the involvement of the ring chromosome and clinical outcome. Our subjects demonstrated the prominent features of this syndrome including mental retardation, hypotonia, motor delay, lack of speech, full eyebrows, and large ears. In addition, two of our subjects had central nervous system malformations and regression. The lack of consistent physical abnormalities in our subjects further supports no consistent phenotype manifestations in this cytogenetic syndrome. The variable clinical manifestations seen in ring chromosome 22 subjects may be associated with loss of chromosome 22 sequences near the telomere or attributed to the genetic background of each subject. Similarly, recessive alleles unmasked by the deletion could also contribute to the phenotype.

Abnormalities, Multiple↗
PubMed2003

Microarray analysis of gene/transcript expression in Prader-Willi syndrome: deletion versus UPD.

BACKGROUND: Prader-Willi syndrome (PWS), the most common genetic cause of marked obesity, is caused by genomic imprinting and loss of expression of paternal genes in the 15q11-q13 region. There is a paucity of data examining simultaneous gene expression in this syndrome. METHODS: We generated cDNA microarrays representing 73 non-redundant genes/transcripts from the 15q11-q13 region, the majority within the PWS critical region and others distally on chromosome 15. We used our custom microarrays to compare gene expression from actively growing lymphoblastoid cell lines established from nine young adult males (six with PWS (three with deletion and three with UPD) and three controls). RESULTS: There was no evidence of expression of genes previously identified as paternally expressed in the PWS cell lines with either deletion or UPD. We detected no difference in expression of genes with known biallelic expression located outside the 15q11-q13 region in all cell lines studied. There was no difference in expression levels of biallelically expressed genes (for example, OCA2) from within 15q11-q13 when comparing UPD cell lines with controls. However, two genes previously identified as maternally expressed (UBE3A and ATP10C) showed a significant increase in expression in UPD cell lines compared with control and PWS deletion subjects. Several genes/transcripts (for example, GABRA5, GABRB3) had increased expression in UPD cell lines compared with deletion, but less than controls indicating paternal bias. CONCLUSIONS: Our results suggest that differences in expression of candidate genes may contribute to phenotypic differences between PWS subjects with deletion or UPD and warrant further investigations.

Adult↗
PubMed2002

Clonality studies in giant cell tumor of bone.

Genetic studies including chromosome analysis, telomere reduction and telomere activity, DNA microsatellites and loss of heterozygosity (LOH) studies have been performed on giant cell tumor (GCT) of bone however whether this primary skeletal neoplasm represents a monoclonal or polyclonal proliferation is unknown. Utilizing a new assay to study the polymorphic human androgen receptor locus (HUMARA), the ratio of maternal inactive X-chromosome to the paternal inactive X (Lyon hypothesis) is determined via a methylation--specific polymerase chain reaction (PCR) technique to detect X-chromosome polymorphisms. Characterization of the genetic tumorigenesis of this unpredictable neoplasm may lend insight into its biological behavior and offer improvements in therapeutic intervention, as new information emerges regarding osteoclastic bone resorption. Seventeen female patients with giant cell tumor of bone had their DNA harvested and their X-chromosome inactivation pattern and polymorphisms determined and compared to control. A polyclonal proliferation pattern was identified in all informative samples studied.

Adult↗
PubMed2002

Omphalocele in three generations with autosomal dominant transmission.

We report a family with nine subjects over three generations affected with an omphalocele requiring surgical intervention within the first few days of life. Because of the vertical transmission and male to male inheritance in our family, we conclude that an autosomal dominant gene caused the omphalocele in the affected family members. The paternal great grandfather of the proband was not clinically affected but produced two children with omphaloceles with different spouses.

Adult↗
PubMed2001

Decreased bone mineral density in Prader-Willi syndrome: comparison with obese subjects.

Bone density, anthropometric data, and markers of bone turnover were collected on 21 subjects diagnosed with Prader-Willi syndrome (PWS) and compared with 9 subjects with obesity of unknown cause. In addition, urinary N-telopeptide levels were obtained in all subjects. N-telopeptides are the peptide fragments of type I collagen, the major bone matrix material. During periods of active bone degradation or high bone turnover, high levels of N-telopeptides are excreted in the urine. However, no significant difference was detected in the urinary N-telopeptide levels when corrected for creatinine excretion (raw or transformed data) between our subjects with obesity or PWS and the observed effect size of the between-group difference was small. Although N-telopeptide levels were higher but not significantly different in the subjects with PWS compared with obese controls, the subjects with PWS had significantly decreased total bone and spine mineral density and total bone mineral content (all P < 0.001). No differences in N-telopeptide levels or bone mineral density were observed between subjects with PWS and chromosome 15q deletion or maternal disomy. Thus, decreased bone mineral density in subjects with PWS may relate to the lack of depositing bone mineral during growth when bones are becoming more dense (e.g., during adolescence), possibly because of decreased production of sex or growth hormones and/or long-standing hypotonia. It may not be caused by loss, or active degradation, of bone matrix measurable by the methods described in this study further supporting the possible need for hormone therapy during adolescence.

Adolescent↗
PubMed2001

Kinetic form discrimination in Prader-Willi syndrome.

Discrimination of the shape of motion-produced forms generated by random elements (i.e. second-order stimuli varying in element density and temporal correlation) was tested in four groups: (1) subjects with Prader-Willi syndrome (PWS), chromosome 15q deletion subtype; (2) subjects with PWS, uniparental maternal disomy (UPD) subtype; (3) equivalent non-PWS controls; and (4) normal controls. The performance of the normal controls exceeded that of all other groups (78% correct, P < 0.009). The PWS deletion (66%) and the equivalent control groups (59%) did not differ (P < 0.95). The UPD group performed significantly less well (38%, P < 0.04) than all the other groups. The performance of the PWS deletion and equivalent control groups is consistent with other data indicating that these populations encounter difficulty meeting the processing demands posed by second-order stimuli. The inferior performance of the UPD group may be attributed to receiving two active alleles of a maternally expressed gene influencing neural development. One candidate is the ubiquitin protein ligase gene (UBE3A), which is maternally expressed only and localized to the 15q region. Other possibilities include the requirement of a paternally expressed gene, residual mosaic trisomy 15 in the brain tissue or complex interactions including specific ratios of differentially spliced gene products.

Adult↗
PubMed2001

Total anomalous pulmonary venous connection and a constellation of craniofacial, skeletal, and urogenital anomalies in a newborn and similar features in his 36-year-old father.

We report on a newborn male born to non-consanguineous parents with total anomalous pulmonary venous connection (TAPVC) and additional findings of malformed ears, hypertelorism, brachyphalangy in the hands, pterygium of the elbows, knees, and wrists, complex lower limb pre-axial polydactyly, tibial shortening, clubfeet, horseshoe kidney and a micropenis. He had a 46,XY karyotype. His 36-year-old father had similar craniofacial and limb anomalies suggesting an autosomal dominant syndrome with variable expression. Our patients may represent the 3rd and 4th examples of a newly-described syndrome by Baraitser et al. [(1997) Clin Dysmorphol 6:111-121] which is distinguished by malformed ears, complex pre-axial polydactyly and tibial aplasia in the lower limbs, severe brachyphalangy in the hands, and a micropenis.

Abnormalities, Multiple↗
PubMed2001

Emergence of compulsive behavior and tantrums in children with Prader-Willi syndrome.

Many adults with Prader-Willi syndrome are affected by behaviors such as tantrums, skin-picking, and compulsions. The nature and extent of these problems suggest more attention be directed to their emergence in childhood. Our purpose was to investigate behavior problems in children with this syndrome and identify the age at which these behaviors emerge. Parents of children with Prader-Willi syndrome, Down syndrome, and those developing typically completed questionnaires. Children with Prader-Willi syndrome exhibited more compulsions, skin-picking, and tantrums than did the other groups. A discriminant analysis of behavior variables derived two statistically significant functions that were interpreted as developmental milestones and problematic behavior. These functions correctly predicted membership for 79% of grouped cases.

Child↗
PubMed2000

Plasma cholecystokinin levels in Prader-Willi syndrome and obese subjects.

The cardinal feature of individuals with Prader-Willi syndrome (PWS) is severe hyperphagia-mediated obesity resulting from a faulty satiety mechanism. PWS is the most common genetic cause of marked obesity. Cholecystokinin (CCK) is a 33-amino-acid peptide found in high levels in the gut and brain involved in mediating the satiety response to meals. Free fatty acids (FFA) are responsible for the stimulation of CCK release after a fatty meal, and CCK and plasma FFA levels rise in tandem in normal individuals. Fasting plasma CCK levels were measured by radio-immunoassay in 33 PWS subjects with a mean age of 22.2 years +/- 8.1 years and 24 obese control subjects without a known cause of their obesity with a mean age of 28.7 years +/- 12.9 years. Consistent with previous findings, neither fasting plasma FFA levels (617.5 versus 486.8 microm/mL) or CCK levels (21.0 versus 19.1 pg/mL) were significantly different in PWS or control subjects, respectively. However, there was a significant correlation between fasting plasma FFA and CCK levels in obese subjects (r = 0. 64, P < 0.01), this correlation was completely lacking in PWS subjects (r = -0.06, P = 0.79). This difference in correlation coefficients constitutes a large effect. There were no significant effects observed for genetic subtypes (15q11-q13 deletion or maternal disomy 15), body mass index, percentage of fat, plasma levels of insulin, C-peptide, glucagon or leptin, age, or gender on CCK levels in our PWS subjects. These results suggest that differences in the peripheral CCK response to FFA levels may be a factor contributing to the altered satiety response in PWS subjects.

Adolescent↗
PubMed2000

Metacarpophalangeal pattern profile analysis in Noonan syndrome.

Metacarpophalangeal pattern (MCPP) analysis is an application of an anthropometric technique that provides a quantitative assessment of the amount and direction of abnormality in the hand skeleton. MCPP analysis was undertaken on 15 individuals (9 males, 6 females) with Noonan syndrome ranging in age from 0.1 to 36 years with a mean age at 11.6 years. The overall average Z score for the MCPP variables was -2.1 and the range was -2.5 (for metacarpal two) and -1.5 (for middle phalanx 5). The average hand pattern variability index, a measure of hand bone length relationships, was abnormal. A Pearsonian correlation analysis was used to assess similarity between the mean pattern and each of the 15 individual patterns. Nine (60%) of the fifteen individuals with Noonan syndrome had significant positive correlations (P < 0.05), indicating homogeneity or similarity in the hand patterns. A stepwise discriminant analysis was performed on Z score data from the individual hand bone measurements on the 15 subjects with Noonan syndrome and 41 healthy controls (24 females, 17 males; mean age = 13.1 years with age range of 9.6 to 18 years). This analysis produced a discriminant function with two MCPP variables (metacarpal 1 and middle phalanx 3) entering into the function and producing a correct classification rate of 93%. The two MCPP variables contributed to the overall difference between individuals with Noonan syndrome and the normative sample. The hand pattern variability index was outside of the normal range, indicating an abnormal MCPP with multivariate analysis. The MCPP analysis may be useful as a tool for diagnosis in screening subjects for Noonan syndrome.

Adolescent↗