Search PubMed⌕ Search

Biomedical subjects

M W Steele

Publications and source records attributed to M W Steele.

At least 37 records · Page 2Linked to original sources
PubMed1991

Assessment of X bends in patients with atypical X chromosome phenotypes.

Several patients with X chromosome structural abnormalities have been more severely affected clinically than expected. Since bends at Xq13-21 have been associated with inactivation, the authors scored bends retrospectively in 62 patients with X chromosome aneuploidy and 21 cases with structural abnormalities of the X chromosome. They found that patients with 2 X inactivation sites where one X was structurally abnormal had significantly fewer cells with X bends than normal 46,XX. In addition, these patients also showed X bends on the normal X more often than would be expected if non-random X inactivation of the abnormal X chromosome was occurring. Five of the 6 patients with a short or long arm deletion or paracentric inversion of Xq were mentally retarded or had other congenital anomalies not usually associated with Turner syndrome. This suggests to them that these clinical findings may be related to interference with X inactivation patterns in cells with a structurally abnormal X chromosome.

Aneuploidy↗
PubMed1990

Chromosome mosaicism in hypomelanosis of Ito.

Our finding of chromosome mosaicism with a ring 22 in a retarded black boy with hypomelanosis of Ito prompted a review of this "syndrome." Most patients have a variety of non-dermal defects, particularly those affecting CNS function. Among karyotyped patients, most are chromosome mosaics of one sort or another. Hypomelanosis of Ito turns out to be a causable non-specific phenotype, i.e., a clinical marker for chromosome mosaicism of all different types in individuals with a dark enough skin to show lighter patches. Consequently, cytogenetic evaluation is indicated in all patients with this skin finding.

Abnormalities, Multiple↗
PubMed1990

Mosaicism in Pallister i(12p) syndrome.

The clinical diagnosis of Pallister syndrome in a 1-day-old white boy was confirmed by the presence of i(12p) in 100% of cells on direct bone marrow analysis. This is the second Pallister syndrome case in which cytogenetic diagnosis was made in bone marrow cells during the neonatal period. Other tissues analyzed in our patient included peripheral blood PHA-stimulated cultured lymphocytes and postmortem skin and lung cultured fibroblasts with 3%, 98.5%, and 97.5% of cells containing the i(12p), respectively. Serial skin fibroblast cultures re-established from frozen cells were analyzed sequentially over time for the isochromosome. There was slight reduction in the proportion of i(12p) cells until passage 15 with plateauing of the proportion of i(12p) cells at about 80% until culture senescence. Our review of such cytogenetic analyses suggests that in vivo and perhaps also in vitro isochromosome loss best explains the intra- and inter-tissue specific chromosomal mosaicism in the i(12p) syndrome. In any event, our results indicate that confirmation of the diagnosis in the neonatal period is possible by direct cytogenetic analysis of bone marrow.

Bone Marrow Cells↗
PubMed1990

X chromosome imprinting in fragile X syndrome.

Laird et al. (1987) hypothesized that there are at least four cis-acting alleles or 'chromosome states' at Xq27 that increasingly delay replication at this chromosomal area resulting in its increasing fragility in vitro. When on the inactive X chromosome, the proposed third ('mutated') allele can permanently block reactivation of its cis Xq27 area as the chromosome passes through female meiosis. Males and some females who inherit such an 'imprinted' fragile X chromosome (the fourth proposed allele) will be clinically affected due to impaired transcription of genes in the 'imprinted' Xq27 area. To test this hypothesis, late replication reverse banding patterns at Xq27 were evaluated in cultured lymphoblastoid cell lines from 25 subjects. Our data suggest that DNA replication of the presumed 'imprinted' Xq27 region in affected fragile X patients is indeed later relative to Xq27 on the active X chromosome in other subjects. These results support in part Laird's hypothesis of chromosomal imprinting in fragile X syndrome.

Chromosome Banding↗
PubMed1989

The fragile X marker and autism in perspective.

Recent reports link the fragile X chromosome abnormality to autism, with the association ranging from 0 to 53%, but the diagnostic criteria for autism were unclear in some of the studies. The need for fragile X chromosome studies in larger populations of autistic children and adults was recognized. In this study, chromosome analyses were performed on 85 carefully diagnosed autistic males, yielding a 2.4% incidence of the fragile X abnormality. It is concluded that the incidence of the fragile X chromosome abnormality in autistic individuals is likely the same as that in the mentally retarded male population and therefore does not increase the risk for autism above that of mental retardation itself.

Adolescent↗
PubMed1988

Interstitial and terminal deletions of the long arm of chromosome 4: further delineation of phenotypes.

We reviewed 45 patients with a deletion of the long arm of chromosome 4. Forty-one were previous reports (25 terminal deletions and 16 interstitial deletions) and 4 are new cases with terminal deletions. Of the 29 patients with terminal deletions, 18 with deletion at 4q31 and 4 at 4q32----qter had an identifiable phenotype consisting of abnormal skull shape, hypertelorism, cleft palate, apparently low-set abnormal pinnae, short nose with abnormal bridge, virtually pathognomonic pointed fifth finger and nail, congenital heart and genitourinary defects, moderate-severe mental retardation, poor postnatal growth, and hypotonia. Six patients with a deletion at 4q33 and one patient with deletion 4q34 were less severely affected. In general, patients with various interstitial deletions proximal to 4q31 had a phenotype that was less specific, although mental retardation and minor craniofacial anomalies were also present. There were 3 patients with piebaldism and one with Rieger syndrome. We conclude that terminal deletion of chromosome 4q (4q31----qter) appears to produce a distinctive malformation (MCA/MR) syndrome in which the phenotype correlates with the amount of chromosome material missing and which differs from the more variable phenotype associated with interstitial deletions of 4q.

Abnormalities, Multiple↗
PubMed1988

Rhabdomyosarcoma in Roberts syndrome.

A 23-month-old child diagnosed as having Roberts syndrome, born to consanguineous parents, developed a sarcoma botryoides. Cytogenetic evaluation of peripheral blood lymphocytes and tumor cells showed premature centromere separation, which is characteristic of Roberts syndrome.

Abnormalities, Multiple↗
PubMed1988

Risk effect of maternal age in Pallister i(12p) syndrome.

Pallister syndrome is consequent to mosaicism for i(12p). The isochromosome is found mainly in skin fibroblast cultures, but rarely also in cultured peripheral blood lymphocytes. Maternal age for reported cases of Pallister syndrome was significantly older (p less than 0.005) compared to maternal age for the general population, and similar to maternal age in cases of Down syndrome (p less than 0.5). Paternal age in cases of Pallister syndrome was that expected in the general population from the age of their spouses (p less than 0.9). These data complement the maternal age effect seen in other aneuploidy conditions and suggest, as is found in mosaic cases of Down syndrome, that the chromosomally normal cell line in Pallister syndrome arises post-conception from a zygote already aneuploid consequent to meiotic nondisjunction.

Adult↗
PubMed1988

Clinical consequences of deletion 1p35.

Few cases of deletion 1p have been reported. We report a case of terminal deletion 1p35 in a patient with psychological and neurological dysfunction.

Autistic Disorder↗
PubMed1988

46XY siblings with inadequate virilization and CNS deficiency.

Familial expression of inadequate virilization of 46XY siblings is often reported as an isolated anomaly. We recently evaluated two families with 2 siblings who had a 46XY karyotype, ambiguous genitalia or micropenis, facial anomalies and mental retardation. There is no evidence of gonadotropin deficiency, defects of steroidogenesis, or androgen insensitivity. While there was a testosterone response to human chorionic gonadotropin stimulation in all 3 tested, gonadotropin levels were elevated in 2 of the infants suggestive of faulty seminiferous tubules, 1 of whom later had elevated luteinizing hormone levels. These kindreds may represent a new syndrome with either an X-linked recessive or sex-limited autosomal dominant form of inheritance, with partial testicular failure, multiple congenital anomalies, and mental retardation.

Cells, Cultured↗
PubMed1987

Increased sister chromatid exchange frequency at Xq27 site in affected fragile X males.

Sister chromatid exchange (SCE) was evaluated in peripheral blood lymphocytes cultured from normal subjects, fragile X carrier females, and fragile X affected males and in general did not differ among all subjects whether cells were grown in thymidine-deficient or complete medium. However, at the Xq27 site, SCE was significantly increased for fragile X affected males, particularly in cells grown in thymidine-deficient medium.

Cells, Cultured↗
PubMed1987

Clinical comparison of 59 Prader-Willi patients with and without the 15(q12) deletion.

Fifty-nine patients with Prader-Willi syndrome (PWS) (including three blacks) were enrolled in a behavior modification program including dietary restriction, nutritional education for self-management of food intake, and exercise. Caloric intake for most patients was 700-800 calories per day. The average stay per patient was 5 weeks with a mean weight loss of 6.6 kg. Thirty-one patients (53%) had apparently normal chromosomes compared to 25 patients (42%) with apparent 15(q12) deletion. Three patients had other chromosome abnormalities including two with mosaicism for idic(15)(q11) and one with a de novo apparently balanced translocation t(8q;18q). There were no differences in manifestations or the effects of the behavior modification program between chromosomally normal and abnormal patients. However, the mean weight loss in the 59 PWS patients was less than would have been expected based on their calculated daily caloric requirements suggesting that PWS patients have reduced caloric needs per unit of body weight compared to normal individuals. Supporting this also was that weight maintenance could be accomplished with only 1000 calories per day on the average. In general, behavioral response to the modification program was successful in that tantrum responses, while not eliminated, were reduced in frequency and severity.

Adolescent↗
PubMed1986

Relative reliability of three different discriminant analysis methods for detecting PKU gene carriers.

A previously derived discriminant function for detecting classical PKU gene carriers without a priori pedigree probability was reevaluated using a large sample size. The test involves fluorometric measurement of fasting phenylalanine and tyrosine plasma levels. Among 75 controls and 45 known carriers, 95% could be classified as to their carrier status with greater than 98% accuracy. The accuracy of our method in classifying our population compared favorably to that of two other discriminant analysis methods requiring a priori probability.

Biometry↗
PubMed1986

Effect of sibship position on reproductive behavior of couples after the birth of a genetically handicapped child.

We compared the reproductive behavior of 132 white married couples of whom 44 had a child with cystic fibrosis, 44 with either Down Syndrome or neural tube defect, and 44 with cerebral palsy to that of the general USA white married population. The three groups of couples were similar respecting race, religion, maternal age, parental occupation and education, and sex of affected child. Most couples had received some genetic counseling and all were followed for at least 3 years after diagnosis of the affected child. Regardless of the degree of recurrent risk and availability or not of prenatal diagnosis, couples were several fold more likely to reproduce again when the affected child was the 1st rather than later born. From this study and others, we conclude that the three major determinators of reproductive behavior in couples after having a genetically handicapped child are the same as those for the general population. Specifically, these are: parental desire for children, past reproductive experiences (that is, sibship size and perhaps also outcome), and maternal age.

Adolescent↗
PubMed1985

A mildly retarded woman with 46,XX/47,XX, + 18 mosaicism.

We describe a mildly retarded woman with trisomy 18 mosaicism. The phenotype did not suggest trisomy 18, but the mild mental retardation, asymmetric face with bushy eyebrows and thick lips, short stature, and older maternal age raised the suspicion of a chromosomal cause for her condition.

Adult↗