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Biomedical subjects

M G Butler

Publications and source records attributed to M G Butler.

At least 127 records · Page 7Linked to original sources
PubMed1990

Prader-Willi syndrome: current understanding of cause and diagnosis.

Prader-Willi syndrome (PWS) is characterized by hypotonia, obesity, hypogonadism, short stature, small hands and feet, mental deficiency, a characteristic face, and an interstitial deletion of the proximal long arm of chromosome 15 in about one-half of the patients. The incidence is estimated to be about 1 in 25,000, and PWS is the most common syndromal cause of human obesity. DNA abnormalities, usually deletions or duplications of chromosome 15, have been identified in individuals with PWS with or without recognizable chromosome 15 deletions. Paternal origin of the chromosome 15 deletion by cytogenetic and DNA studies has been found in nearly all PWS individuals studied. No cytogenetic evidence for chromosome breakage has been identified, although an environmental cause (e.g., paternal hydrocarbon-exposed occupations) of the chromosome 15 abnormality has been proposed. PWS patients with the chromosome 15 deletion are more prone to hypopigmentation compared with PWS individuals with normal chromosomes, but no other clinical differences are consistently identified between those with and without the chromosome deletion. Anthropometric, dermatoglyphic, and other clinical findings indicate homogeneity of PWS patients with the chromosome deletion and heterogeneity of the nondeletion patients. A review of our current understanding of the major clinical, cytogenetic, and DNA findings is presented, and clinical manifestations and cytogenetic abnormalities are summarized from the literature.

Anthropometry↗
PubMed1990

Chromosome lesions which could be interpreted as "fragile sites" on the distal end of Xq.

Chromosome lesions which could be interpreted as "fragile sites" on the distal end of the long arm of the X chromosome were identified during a cytogenetic study of 160 mentally retarded adult males with no apparent cause of their mental retardation and one normal adult female with a family history of fra (X) syndrome. Peripheral blood samples were cultured in either M199 or RPMI 1640 medium with FUdR or BrdU. Metaphases were examined for chromosome lesions or fragile sites on the distal end of Xq and 3 distinct sites were observed: Xq26, Xq27.2, and Xq27.3. Other chromosome lesions at Xq28 were observed and interpreted as nonspecific telomeric structural changes. Chromosome lesions were observed in cells from 14 of the 161 individuals. These included: 5 patients with an Xq26 site, 2 with the recently reported Xq27.2 site, 4 with the Xq27.3 site (characteristic of the fra (X) syndrome), 2 with nonspecific telomeric structural changes, and one individual with 2 lesions (a nonspecific telomeric structural change and an Xq26 site). Additional research is necessary to determine the frequency and clinical significance, if any, of lesions occurring in this region of the X chromosome and to distinguish among heritable fragile sites, constitutive fragile sites, and nonspecific telomeric structural changes.

Adolescent↗
PubMed1990

Antibodies to cardiolipin and intermediate filaments: a study of autoimmunity in rheumatoid arthritis.

Autoantibodies to cardiolipin and intermediate filaments have both been reported with increased frequency in rheumatoid arthritis. We evaluated the frequency, pathological significance, and diagnostic relevance of these autoantibodies in a series of 124 patients and controls. We studied 81 patients with rheumatoid arthritis, 23 with osteoarthritis, and 20 normals. Antibodies to cardiolipin were measured by an ELISA method and antibodies to intermediate filaments were measured by indirect immunofluorescence using HEp2 cells. Antibodies to cardiolipin were present in 58% of rheumatoid patients and antibodies to intermediate filaments were present in 55% rheumatoid patients. They were both predominantly of IgM class, and were more frequent than in normal or osteoarthritic controls. Correlating levels of both these autoantibodies to clinical and laboratory measures of disease activity such as Ritchie articular index and C-reactive protein level showed that no consistent relationships existed. They were not related to other auto-antibodies such as rheumatoid factors and anti-nuclear antibodies, nor to each other. These results show that antibodies to cardiolipin and intermediate filaments in rheumatoid arthritis are of no diagnostic value, they are not related to disease activity, and have no relationship to other autoimmune disturbances. We suggest that several pathological mechanisms must be involved in the development of autoantibodies in rheumatoid arthritis.

Adult↗
PubMed1990

Focal sclerosing glomerulonephritis in a child with Laurence-Moon-Biedl syndrome.

We report a 6-year-old white male with Laurence-Moon-Biedl syndrome and focal sclerosing glomerulonephritis (FSGN). To our knowledge, FSGN has not been reported previously in patients with this syndrome. We wish to alert the clinician to the wide variety of renal abnormalities that can be seen in patients with this rare, autosomal recessive disorder.

Biopsy↗
PubMed1989

Genetic imprinting suggested by maternal heterodisomy in nondeletion Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is the most common form of dysmorphic genetic obesity associated with mental retardation. About 60% of cases have a cytological deletion of chromosome 15q11q13 (refs 2, 3). These deletions occur de novo exclusively on the paternal chromosome. By contrast, Angelman syndrome (AS) is a very different clinical disorder and is also associated with deletions of region 15q11q13 (refs 6-8), indistinguishable from those in PWS except that they occur de novo on the maternal chromosome. The parental origin of the affected chromosomes 15 in these disorders could, therefore, be a contributory factor in determining their clinical phenotypes. We have now used cloned DNA markers specific for the 15q11q13 subregion to determine the parental origin of chromosome 15 in PWS individuals not having cytogenetic deletions; these individuals account for almost all of the remaining 40% of PWS cases. Probands in two families displayed maternal uniparental disomy for chromosome 15q11q13. This is the first demonstration that maternal heterodisomy--the presence of two different chromosome 15s derived from the mother--can be associated with a human genetic disease. The absence of a paternal contribution of genes in region 15q11q13, as found in PWS deletion cases, rather than a mutation in a specific gene(s) in this region may result in expression of the clinical phenotype. Thus, we conclude that a gene or genes in region 15q11q13 must be inherited from each parent for normal human development.

Alleles↗
PubMed1989

Analysis of chromosome breakage in the Prader-Labhart-Willi syndrome.

Analysis of chromosome breakage with mitomycin C (MMC) and folate-deficient culture conditions was undertaken on 18 Prader-Labhart-Willi syndrome (PLWS) patients (10 with 15q12 deletion [5 females, 5 males; mean age = 17.9 yr, range of 0.3 to 40 yr] and 8 without deletion [2 females, 6 males; mean age = 18.6 yr, range of 7 to 26 yr]), 21 PLWS parents with an average age of 39.2 yr and a range of 25 to 70 yr (12 fathers [8 fathers of PLWS children with the 15q12 deletion and 4 fathers of PLWS children with normal chromosomes] and 9 mothers [4 mothers of PLWS children with the 15q12 deletion and 5 mothers of PLWS children with normal chromosomes]), and age-matched control individuals. There was no difference between PLWS patients and control individuals in the number of chromosome and chromatid aberrations in cells grown at 48 and/or 96 hr in either 20 ng/ml or 50 ng/ml of MMC or between the PLWS parents and control individuals in cells grown in 50 ng/ml MMC for 96 hr, although a small increase (P less than 0.05) in chromosome breakage was found in cells from the total PLWS parental group compared with control individuals exposed for 48 hr in 50 ng/ml MMC. There was also no significant difference in chromosome fragile site frequency in cells grown in folate-deficient culture conditions in PLWS patients, their parents, or controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Effects of age, sex and multiple endocrine neoplasia type-II on silver stained nucleolar organizer regions.

Silver stained nucleolar organizer regions (AgNORs) were studied in phytohemagglutinin (PHA)-stimulated lymphocytes from 55 Caucasian control individuals (34 females with average age of 24 years and age range 19 weeks gestation to 87 years; 21 males with average age of 31 years and age range 29 weeks gestation to 72 years) and 13 individuals (7 females, 6 males; average age 38.8 years with age range 25-58 years) with multiple endocrine neoplasia-type II (MEN-II), an autosomal dominant malignancy with increased chromosome breakage. For the first time, AgNORs were examined in lymphocytes from normal fetuses and patients with MEN-II in order to determine the effects of age, sex or malignancy on the number of AgNORs. No significant difference in the average number of AgNORs were found in fetal cells (8.2 +/- S.D. 0.7/cell) when compared with cells from older individuals including those over 65 years of age (8.0 +/- S.D. 0.8/cell). There was a statistically significant negative correlation (P less than 0.05) between the modal number of AgNORs on G but not D chromosomes in both males and females. A negative correlation was also found between the mean number of AgNORs and age but was not statistically significant. The average number of AgNORs in the MEN-II individuals was 8.5 +/- S.D. 0.7/cell, which was not significantly different than 8.2 +/- S.D. 0.7/cell observed in age-matched control subjects.

Adolescent↗
PubMed1989

Prenatal diagnosis and carrier detection of a cryptic translocation by using DNA markers from the short arm of chromosome 5.

DNA markers from the short arm of chromosome 5 were used to examine a large family in which a microscopically undetectable translocation was segregating. In addition to confirming that three retarded children were hemizygous for loci distal to 5p14, these analyses identified five individuals as being carriers of the balanced translocation. The use of molecular probes provided informed genetic counseling to the family for the first time. With the DNA markers from 5p, prenatal diagnosis was performed on two fetal chorionic villus samples, both of which were found to have unbalanced karyotypes. The identification of translocation carriers was complicated by recombination between the small translocated segment of 5p and the corresponding region on the normal homologue, which changed the haplotype of the translocated 5p segment.

Animals↗
PubMed1989

Occupational hydrocarbon exposure among fathers of Prader-Willi syndrome patients with and without deletions of 15q.

Prader-Willi syndrome (PWS) is a multiple-anomaly disorder in which 50%-70% of cases are associated with a de novo interstitial deletion [del 15(q11-13)] on prometaphase cytogenetic analysis, the remainder having apparently normal chromosomes. In most instances, the paternally derived chromosome has become deleted in the affected child, suggesting the possibility of a predisposing environmental factor. Strakowski and Butler found an increased incidence of paternal periconceptional employment in hydrocarbon-exposing occupations in this population. This observation may suggest a causal relationship to PWS. To determine whether this association may distinguish the cytogenetically different groups, we identified 81 patients with the disorder who were physically and cytogenetically examined in three centers, and we compared the frequency of possible periconceptional occupational hydrocarbon exposure between fathers of patients who demonstrate a 15q deletion and those who do not. There was no statistically significant difference between the cytogenetically different groups. In both groups, approximately half of the fathers had been employed in hydrocarbon-exposing jobs. These findings suggest lack of etiologic heterogeneity between the cytogenetically different groups for PWS and affirm the need to seek submicroscopic deletions through molecular genetic studies. These data also provide additional evidence that hydrocarbon exposure among fathers of children with PWS may be causally related to the disorder, and they also suggest the need for more accurate assessment of exposure via a large, controlled study.

Adolescent↗
PubMed1989

Hypopigmentation: a common feature of Prader-Labhart-Willi syndrome.

In order to determine the frequency and characterization of hypopigmentation in Prader-Labhart-Willi syndrome (PLWS), clinical, cytogenetic and biochemical findings are reported in 56 PLWS individuals. Forty-eight percent of the individuals with PLWS met the criteria for hypopigmentation. Hypopigmentation in PLWS individuals appears to be as common as previously recognized features such as behavioral problems and dental abnormalities. Significant differences in hair color, sun sensitivity, and complexion were found between those PLWS patients with the chromosome 15 deletion and those with normal chromosomes. Individuals with the deletion frequently had lighter hair color, more sun sensitivity, and fairer complexion than did either other family members or nondeletion PLWS patients. No significant differences in biochemical findings (phenylalanine, tyrosine, catecholamines, or beta-melanocyte-stimulating hormone) were found between deletion and nondeletion PLWS patients or between hypopigmented and normally pigmented patients. The data suggest that a gene(s) controlling the activity of tyrosinase or other enzymes required for melanin production is located on proximal 15q.

Adolescent↗
PubMed1988

Metacarpophalangeal pattern profile analysis in Sotos syndrome: a follow-up report on 34 subjects.

Metacarpophalangeal pattern profile (MCPP) was determined on 34 Sotos syndrome individuals and compared with previous MCPP studies. The mean hand profile contained a major peak in the proximal phalangeal area and a smaller peak in the metacarpal area, while the distal hand bones were relatively short. There appear to be three recognized hand profiles in Sotos syndrome, which suggests heterogeneity of the syndrome, although correlation studies indicate clinical homogeneity of individuals in the younger age groups. Discriminant analysis of Sotos syndrome versus control subjects produced a function of two MCPP variables, plus age, which may be applied as another diagnostic tool.

Abnormalities, Multiple↗
PubMed1988

Two patients with ring chromosome 15 syndrome.

We report on 2 patients (3 1/2 year-old-male and 6-year-old female) with the ring 15 chromosome syndrome and speech delays and review 25 cases from the literature. The main characteristics of this syndrome include growth retardation (100%), variable mental retardation (95%), microcephaly (88%), hypertelorism (46%), and triangular facies (42%). Other frequent findings include delayed bone age (75%), brachydactyly (44%), speech delay (39%), frontal bossing (36%), anomalous ears (30%), café-au-lait spots (30%), cryptorchidism (30%), and cardiac abnormalities (30%). The average age at diagnosis was 8.1 years. The average maternal and paternal age at the time of birth was 28 and 31 years, respectively.

Abnormalities, Multiple↗
PubMed1988

Acrodysostosis: report of a 13-year-old boy with review of literature and metacarpophalangeal pattern profile analysis.

We report on a 13-yr-old boy with acrodysostosis, a review of 30 cases in the literature, and metacarpophalangeal pattern profile (MCPP) analysis. The prominent manifestations (present in greater than 75% of cases) of this condition include nasal and maxillary hypoplasia, peripheral dysostosis, first ray hyperplasia of the foot, acromesomelic brachymelia, decreased interpedicular distance, advanced skeletal maturation and mental retardation. Results of chromosome studies have been normal. An autosomal dominant inheritance pattern was reported in two families. Maternal and paternal ages were 2 and 3 yr, respectively, above the average age of the general parent population, which suggests that advanced parental age may be a factor in the cause of this condition. A characteristically abnormal MCPP was found in our patient and in 16 additional cases studied from the literature. A mean MCPP was developed for the syndrome. MCPP analysis may be useful as a diagnostic tool in patients suspected to have acrodysostosis.

Adolescent↗