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Biomedical subjects

M G Butler

Publications and source records attributed to M G Butler.

At least 37 records · Page 2Linked to original sources
PubMed2000

SPONASTRIME dysplasia: report of an 11-year-old boy and review of the literature.

SPONASTRIME (SPOndylar and NAsal changes, with STRIations of the MEtaphyses) dysplasia is a rare, autosomal recessive bone disorder first described by Fanconi et al. [1983: Helv Paediatr Acta 38:267-280]. Radiographic findings include abnormal vertebral bodies with age-dependent changes, and striations of the metaphyses, scoliosis, and retarded ossification of the carpal bones. Physical features include severe short stature, lumbar lordosis, midface hypoplasia, frontal bossing, and a depressed nasal root. To date, 12 patients from 6 families have been reported. Four additional patients have been reported with a variant of this condition, which includes mental retardation. We report on an 11-year-old boy with features consistent with SPONASTRIME dysplasia. Height was 106.1 cm (-6 SD). He had a coarse appearing face with a depressed nasal bridge, short, upturned nose, and midface hypoplasia. Intelligence was normal. A clinical evaluation at 6 years of age suggested the diagnosis of spondyloepiphyseal dysplasia (SED). However, genetics evaluation at 11 years of age with repeat radiologic studies revealed delayed carpal ossification (-4 to -5 SD), metaphyseal irregularities and striations most notably in the distal femurs and the proximal tibias, lumbar lordosis, narrow interpedicular distances of the lumbar spine, and pear-shaped vertebral bodies. These findings were most consistent with the diagnosis of SPONASTRIME dysplasia, and not SED. Although radiographic findings of SPONASTRIME dysplasia are distinguishable from SED, the physical appearance may be similar. Many bone dysplasias have overlapping radiographic findings and clinical presentation but with different recurrence risks, making genetic counseling a challenge.

Adolescent↗
PubMed2000

Microsatellite instability in sacral chordoma.

BACKGROUND AND OBJECTIVES: Microsatellite instability (MIN) is an indirect marker of globally defective DNA mismatch repair in the neoplastic cells of cancer patients. Chordomas are rare, primary skeletal malignancies for which few characteristic molecular genetic markers have been identified. Is MIN demonstratable in chordoma? METHODS: We evaluated sacral chordomas from 12 patients with sacral chordomas for the presence of MIN at 9 different genetic loci from chromosomes 1p, 5q, 7q, 9p, 11p, 12p, 13q, 17p, and 18q. Cells were scraped from glass slides so that tumor and control DNA could be isolated and then amplified by polymerase chain reaction (PCR). Heterozygosity indices were >/= 0.70. RESULTS: Six patients (50%) demonstrated MIN for at least 1 locus, and 2 patients demonstrated loss of heterozygosity (LOH) for at least 1 locus. Only 1 individual's chordoma manifested microsatellite instability (MIN) and loss of heterozygosity (LOH). Another patient manifested no MIN but LOH at 9p and 18q. Interestingly, this individual had the most aggressive clinical cancer course, presenting with lymph node metastasis and succumbing to widespread metastatic disease. CONCLUSIONS: Chordomas can be added to the list of malignancies demonstrating MIN. LOH may prove to portend a worse prognosis than MIN when more tumors are examined.

Adult↗
PubMed2000

Appetitive behavior, compulsivity, and neurochemistry in Prader-Willi syndrome.

Advances in genetic research have led to an increased understanding of genotype-phenotype relationships. Excessive eating and weight gain characteristic of Prader-Willi syndrome (PWS) have been the understandable focus of much of the research. The intense preoccupation with food, lack of satiation, and incessant food seeking are among the most striking features of PWS. It has become increasingly clear that the behavioral phenotype of PWS also includes symptoms similar to obsessive compulsive disorder, which in all probability interact with the incessant hunger and lack of satiation to engender the intense preoccupation and food seeking behavior that is characteristic of this disorder. Several lines of evidence suggest that genetic material on chromosome 15 may alter synthesis, release, metabolism, binding, intrinsic activity, or reuptake of specific neurotransmitters, or alter the receptor numbers and/or distribution involved in modulating feeding. Among the likely candidates are GABAnergic, serotonergic, and neuropeptidergic mechanisms. This review summarizes what is known about the appetitive behavior and compulsivity in PWS and discusses the possible mechanisms underlying these behaviors. MRDD Research Reviews 2000;6:125-130.

Brain↗
PubMed2000

Intellectual characteristics of Prader-Willi syndrome: comparison of genetic subtypes.

Advances in genetics have led to an increased understanding of the role of the genotype on behavioural functioning. The purpose of the present study was to examine differences in intellectual functioning in individuals with Prader-Willi syndrome (PWS) with a paternal 15q11-q13 deletion versus maternal uniparental disomy (UPD) of chromosome 15. Measures of intelligence and academic achievement were administered to 38 individuals with PWS (24 with deletion and 14 with UPD). The subjects with UPD had significantly higher verbal IQ scores than those with deletion (P< 0.01). The magnitude of the difference in verbal IQ was 9.1 points (69.9 versus 60.8 for UPD and deletion PWS subjects, respectively). Only 17% of subjects with the 15q11-q13 deletion had a verbal IQ > or = 70, while 50% of those with UPD had a verbal IQ > or = 70. Performance IQ scores did not differ between the two PWS genetic subtype groups. This is the first report to document the difference between verbal and performance IQ score patterns among subjects with PWS of the deletion versus the UPD subtype.

Adolescent↗
PubMed2000

Specific genetic diseases at risk for sedation/anesthesia complications.

UNLABELLED: We reviewed of a number of genetic diseases known or at risk for sedation or anesthesia complications. Some of these conditions are relatively common (e.g., Down's syndrome) whereas others are rare or present with multiple congenital anomalies that have an impact on health care delivery. We listed complications, recommended presedation evaluations, and included checklist items to assist the health care provider administering sedation and anesthesia. A better recognition and awareness of risk factors associated with specific genetic diseases should lessen the likelihood of complications during these procedures. IMPLICATIONS: This article provides a brief description of potential problematic genetic disorders and associated complications that may manifest during sedation or anesthesia. Recommendations for presedation evaluation and checklist items are given that may impact on the delivery of care for these patients.

Abnormalities, Multiple↗
PubMed2000

Intercontinental karyotypic differentiation of Chironomus entis Shobanov, a Holarctic member of the C. plumosus group (Diptera, Chironomidae).

Analysis of banding sequences of polytene chromosomes in Palearctic (Russian) and Nearctic (North American) Chironomus entis shows strong karyotype divergence between populations on the two continents. Four out of seven chromosomal arms in the North American C. entis karyotype are characterized by sequences found only in the Nearctic. In total, 44 banding sequences are now known for this species across the Holarctic, including 22 exclusively Palearctic, 6 Holarctic, and 16 exclusively Nearctic sequences. The degree of cytogenetic differentiation between Palearctic and Nearctic C. entis populations is an order of magnitude greater than differentiation among populations within either continent, but is only one third as great as the cytogenetic distance between the sibling species C. entis and C. plumosus. C. entis is the only sibling species of C. plumosus uncovered during cytological identification of Chironomus species from more than 50 North American lakes, indicating that the plumosus sibling-species group is much smaller in the Nearctic than in the Palearctic, where a dozen sibling species are known. Cytogenetic distance values calculated between Nearctic and Palearctic representatives of both C. entis and its sibling species C. plumosus are similar, but result from different patterns of karyotype divergence. New World C. entis is distinguished from Old World populations by the 16 uniquely Nearctic sequences, four of which occur in the homozygous state. In contrast, North American C. plumosus has fewer uniquely Nearctic sequences, and only one that occurs as a homozygote. However, four chromosomal arms in C. plumosus that are polymorphic in the Palearctic show fixation, or near fixation, of Holarctic sequences in the Nearctic C. plumosus karyotype. Thus, both the fixation of Holarctic sequences, and the occurrence or fixation of distinctly Nearctic sequences, contribute significantly to karyotype divergence. Patterns of karyotype divergence in Palearctic and Nearctic populations of different Holarctic chironomid species are discussed relative to intercontinental cytogenetic differentiation in other dipterans.

Animals↗
PubMed2000

Adenovirus keratitis: a role for interleukin-8.

PURPOSE: Adenovirus type 19 (Ad19) infection of the human cornea results in a chronic, multifocal, subepithelial keratitis. Existing evidence suggests that early subepithelial corneal infiltrates are composed of polymorphonuclear neutrophils. In this study, the capacity of Ad19-infected human corneal stromal fibroblasts (HCFs) to produce neutrophil chemotactants (chemokines) was tested. METHODS: HCFs grown from human donor corneas and passaged thrice were infected with a corneal isolate of Ad19 or mock-infected with virus-free media. Bioactivity of the cell supernatants was tested by a neutrophil chemotaxis assay. Supernatants were assayed by enzyme-linked immunosorbent assay for the neutrophil chemotactants interleukin-8 (IL-8) and GRO-alpha. Corneal facsimiles were generated with HCFs and collagen type I, infected with Ad19, and assayed by immunohistochemistry. RESULTS: Ad19 infection of HCFs increased neutrophil chemotaxis from a baseline of 0.4+/-0.7 cells/high-powered field (hpf; mock-infected) to 21.8+/-2.3 cells/hpf (Ad19-infected). Chemotaxis was reduced by the addition of neutralizing antibodies against IL-8 and GRO-alpha. Infection of HCFs induced quantities of IL-8 protein 300- and 1000-fold over mock-infected controls at 4 and 24 hours, respectively (33 versus 11,813 pg/mL at 4 hours, and 57 versus 76,376 pg/mL at 24 hours, P< or = 0.001 for both). In contrast, GRO-alpha protein levels were only sevenfold higher at 24 hours postinfection (118 pg/mL in mock-infected controls versus 880 pg/mL in Ad19-infected cell supernatants). Neither chemokine was induced by infection of an immortalized human corneal epithelial cell line. Immunohistochemistry of infected corneal facsimiles demonstrated IL-8 in the extracellular matrix within 3 days after infection. CONCLUSIONS: Production of chemokines in infected tissues facilitates an early innate immune response to infection, and in the infected corneal stroma represents an elementary defense mechanism. Interleukin-8 may play a role in the development of subepithelial infiltrates in adenovirus keratitis.

Adenoviridae↗
PubMed1999

Screen for MAOA mutations in target human groups.

Brunner et al. [1993: Am J Hum Genet 52: 1032-1039; 1993: Science 262:578-580] described males with an MAO-A deficiency state resulting from a premature stop codon in the coding region of the MAOA gene. This deficiency state was associated with abnormal levels of amines and amine metabolites in urine and plasma of affected males, as well as low normal intelligence and apparent difficulty in impulse control, including inappropriate sexual behavior. In the present study, disruption of the MAOA gene was evaluated in males with mental retardation with and without a history of sexually deviant behavior, as well as normal controls, healthy males, and patients with other diseases (Parkinson disease, Lesch-Nyhan syndrome). When available, plasma samples were evaluated first for levels of 3-methoxy, 4-hydroxyphenolglycol (MHPG), a metabolite of norepinephrine which serves as the most sensitive index of MAO-A activity in humans. Blood DNA from individuals with abnormally low MHPG, and from other individuals for whom metabolite levels were not available, were screened for nucleotide variations in the coding region of the MAOA gene by single-strand conformational polymorphism (SSCP) analysis across all 15 exons and splice junctions, and by sequencing, when indicated by either altered metabolites or SSCP shifts. No evidence for mutations disrupting the MAOA gene was found in 398 samples from the target populations, including institutionalized mentally retarded males (N = 352) and males participating in a sexual disorders clinic (N = 46), as well as control groups (N = 75). These studies indicate that MAOA deficiency states are not common in humans.

Adult↗
PubMed1999

Development and validation of a measurement system for assessment of energy expenditure and physical activity in Prader-Willi syndrome.

OBJECTIVE: The morbid obesity associated with Prader-Willi syndrome (PWS) may result from either excessive energy intake or reduced energy expenditure (EE). In this report, we describe the development and validation of an Activity-Energy Measurement System (AEMS) to measure EE and physical activity components in an environment approximating free-living conditions. RESEARCH METHODS AND PROCEDURES: The AEMS consists of a live-in, whole-room indirect calorimeter equipped with a novel force platform floor system to enable simultaneous measurements of EE, physical activity, and work efficiency during spontaneous activities and standardized exercises. Free-living physical activity and estimated free-living EE are measured using portable triaxial accelerometers individually calibrated in each subject during their stay in the AEMS. RESULTS: Representative data from two PWS patients and two matched control (CTR) subjects displayed EE during their inactive lifestyles. DISCUSSION: This combination of methods will allow the quantification of daily EE and its components, the amount and energy cost of physical activity, and the relationships between body composition and EE, in order to determine their roles in the development and maintenance of the morbid obesity in PWS.

Adolescent↗
PubMed1999

Plasma leptin concentrations in lean and obese human subjects and Prader-Willi syndrome: comparison of RIA and ELISA methods.

Immunoassays for circulating leptin are important research tools for examining the role and regulation of leptin expression in human obesity. However, uncertainty exists regarding the comparability between studies of reported plasma or serum leptin concentrations. The purpose of the present study was to directly compare plasma leptin concentrations by using two of the most widely reported immunoassay methods-namely, a commercially available radioimmunoassay (RIA) and a proprietary enzyme-linked immunosorbent assay (ELISA). Plasma leptin concentrations were measured in healthy lean and obese volunteers and in patients with Prader-Willi syndrome (PWS). Over a wide range of plasma concentrations (2 to 70 ng/mL), leptin measurements obtained with the RIA and ELISA methods were highly correlated (r = 0.957, P<.0001) and were essentially indistinguishable. Leptin levels measured by RIA and ELISA were highly correlated with body mass index (BMI) overall (r = 0.784, P<.0001 and r = 0.732, P<.0001, respectively) and in the lean and obese subgroups. When compared with the results in the lean individuals (mean +/- SEM, 11.6+/-3.2 ng/mL), plasma leptin was significantly higher in both the obese (35.5+/-4.0 ng/mL, P<.0001) and the PWS subjects (30.7+/-6.9 ng/mL, P<.05). However, after we controlled for differences in BMI, the leptin levels were similar in all three groups. In conclusion, we found that the RIA and ELISA used in the present study yield plasma leptin concentrations that are essentially indistinguishable. Our findings should facilitate comparisons of leptin levels measured by these two widely used immunoassays in previous and future studies that examine the role of leptin in body weight regulation.

Adult↗
PubMed1999

Imprinting-mutation mechanisms in Prader-Willi syndrome.

Microdeletions of a region termed the "imprinting center" (IC) in chromosome 15q11-q13 have been identified in several families with Prader-Willi syndrome (PWS) or Angelman syndrome who show epigenetic inheritance for this region that is consistent with a mutation in the imprinting process. The IC controls resetting of parental imprints in 15q11-q13 during gametogenesis. We have identified a larger series of cases of familial PWS, including one case with a deletion of only 7.5 kb, that narrows the PWS critical region to <4. 3 kb spanning the SNRPN gene CpG island and exon 1. Identification of a strong DNase I hypersensitive site, specific for the paternal allele, and six evolutionarily conserved (human-mouse) sequences that are potential transcription-factor binding sites is consistent with this region defining the SNRPN gene promoter. These findings suggest that promoter elements at SNRPN play a key role in the initiation of imprint switching during spermatogenesis. We also identified three patients with sporadic PWS who have an imprinting mutation (IM) and no detectable mutation in the IC. An inherited 15q11-q13 mutation or a trans-factor gene mutation are unlikely; thus, the disease in these patients may arise from a developmental or stochastic failure to switch the maternal-to-paternal imprint during parental spermatogenesis. These studies allow a better understanding of a novel mechanism of human disease, since the epigenetic effect of an IM in the parental germ line determines the phenotypic effect in the patient.

Adult↗
PubMed1999

Self-injurious behavior and Prader-Willi syndrome: behavioral forms and body locations.

With few exceptions (e.g., Lesch-Nyhan syndrome), the specific nature of self-injury in relation to identified genetic syndromes associated with mental retardation is poorly understood. In the present study we surveyed the families of 62 persons with Prader-Willi syndrome to determine the prevalence, topographies, and specific body locations of self-injurious behavior. Self-injury was reported for 81% of the participants. Skin-picking was the most prevalent form, with the front of the legs and head being disproportionately targeted as preferred self-injury body sites. Individuals with the 15q11-q13 deletion injured significantly more body sites than did individuals with maternal disomy 15. Results are discussed in relation to previous self-injury body site findings and implications for the relevance of syndrome-specific behavioral phenotypes.

Adolescent↗
PubMed1999

Extensive analysis of mosaicism in a case of Turner syndrome: the experience of 287 cytogenetic laboratories. College of American Pathologists/American College of Medical Genetics Cytogenetics Resource Committee.

OBJECTIVE: To assemble and interpret karyotype data provided as part of the College of American Pathologists/American College of Medical Genetics Cytogenetics Proficiency Testing Program. DATA SOURCES, EXTRACTION, AND SYNTHESIS: The Cytogenetics Resource Committee requested data on all cells analyzed in a 1994 whole-blood specimen challenge. In that study, 287 participating laboratories analyzed a total of 14297 cells derived from a sample drawn from an adult donor with Turner syndrome. This individual had previously been found to have mosaicism, including cell lines with X structural anomalies along with monosomy X, making this an excellent challenge for a multicenter cytogenetic survey. RESULTS AND CONCLUSIONS: Analysis of the data from this extensive study revealed mosaicism of up to 10 different sex chromosome complements involving the X chromosome with and without a small ring X or a derivative X chromosome. In the routine cytogenetic analysis performed by the participating laboratories, cell lines observed, in decreasing order of prevalence, included 45,X (n = 8357 cells), 46,X,r(X) (n = 3597), 46,X,der(X)t(X;X) (n = 2237), 46,XX (n = 93), 47,X,r(X),r(X) (n = 5), 47,X,der (X)t(X;X),der(X)t(X;X) (n = 3), 47,XX,r(X) (n = 2), and one observation each of 47,XX,der(X)t(X;X), 47,X,der(X)t (X;X),r(X), and 47,XXX. Our molecular cytogenetic data, as well as detailed analysis of G-banded chromosomes, suggest the nomenclature for these 2 abnormal X chromosomes as r(X)(p11.3q21.3) and der(X)t(X;X)(p11.3;q21.3), and we discuss models for the concomitant formation of these 2 entities. Both the degree of analysis and the extensive mosaicism that was discovered in this study are exceptional, and similar reported cases as well as possible mechanisms for the observed X chromosome instability are reviewed.

Adult↗
PubMed1999

Marshall-Smith syndrome: case report of a newborn male and review of the literature.

Marshall-Smith syndrome is a rare congenital condition, characterized by advanced bone age, facial anomalies and relative failure to thrive. We report a newborn male with Marshall-Smith syndrome and summarize 21 previously reported cases. We report cerebellar hypoplasia in our patient, which has not been previously reported in subjects with this rare syndrome. This patient's findings broaden the phenotypic spectrum seen in Marshall-Smith syndrome.

Abnormalities, Multiple↗
PubMed1998

Methylation PCR analysis of Prader-Willi syndrome, Angelman syndrome, and control subjects.

We report on a relatively large survey of Prader-Willi syndrome, Angelman syndrome, and control subjects with the newly described methylation polymerase chain reaction (PCR) method to determine its usefulness for molecular diagnosis. Sixty-one Prader-Willi syndrome (PWS) individuals (26 men and 35 women), 9 Angelman syndrome (AS) patients (5 men and 4 women), and 58 other individuals were studied with methylation PCR following sodium bisulfite treatment of genomic DNA. In addition, multiple tissues, including fetal tissue, were studied from several individuals to determine the effects of various tissues on methylation PCR results. The expected methylation PCR result was observed in each case. This PCR-based assay evaluates the methylation status of the CpG island of the SNRPN gene and allows for rapid molecular diagnosis of PWS or AS with less labor than Southern hybridization for methylation analysis. The PCR results were identical to those achieved by Southern hybridization in those individuals studied.

Angelman Syndrome↗