Esterase D studies in human retinoblastoma.
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Carboxylesterase↗
Biomedical subjects
R S Sparkes
Publications and source records attributed to R S Sparkes.
Segregation and linkage analyses in families of patients with bipolar, unipolar, and schizoaffective mood disorders.
Hypotheses of single major locus transmission (autosomal and X chromosome) of major affective disorder (i.e., bipolar, unipolar, and schizoaffective) are tested using the Elston-Stewart likelihood method of pedigree segregation analysis. The sample consists of families of varying size ascertained through patients treated at the National Institute of Mental Health in Bethesda, Maryland. We test hypotheses on subsamples of families according to: (1) diagnosis of proband (75 bipolar I, 22 bipolar II, 18 unipolar, and six schizoaffective); (2) extreme value of a biological trait in the proband ("low" monoamine oxidase, "low" cerebrospinal fluid serotonin metabolite 5-HIAA); and (3) positive response to lithium in the proband. We cannot find evidence for single major locus transmission of major affective disorder from segregation analysis in any subsample of family even when the diagnostic classification of ill phenotypes is widened to include possible affective "spectrum" diagnoses. In addition, linkage studies of 21 autosomal markers do not provide evidence for single major locus transmission of illness. The maximum lod score, found for 30 families at the MNS locus, was 1.39 at 20% recombination.
Alleles↗
Brief clinical report: the dup(17p) syndrome.
In a 42-month-old girl a duplicated 17p chromosome anomaly was identified by trypsin-Giemsa banding techniques. The clinical findings are compared with those of previous case reports. Common phenotypics changes include failure to thrive; hypoplastic, apparently low-set ears; micrognathia; flexion abnormalities of fingers; and foot abnormalities.
Abnormalities, Multiple↗
Linkage analysis with the trismus-pseudocamptodactyly syndrome.
In 6 generations of a family with the trismus-pseudocamptodactyly syndrome (TPS), we identified 53 affected individuals, 33 females and 23 males. Thirty-one of the 53 were personally examined, as were 77 unaffected relatives. The clinical findings are compared with those of previous reports. Severity of expression is highly variable, but reduced penetrance was not observed. We obtained blood specimens for linkage analysis on all 108 examined individuals. Linkage could be excluded for 16 polymorphic marker loci. The largest positive lod scores were for the BF and AK1 marker systems, being 0.9 and 0.6, respectively. Since BF and AK1 are on different chromosomes (6 and 9, respectively), these results do not indicate a location for the TPS gene.
Child, Preschool↗
A 15 leads to 1 translocation in a patient mosaic for presence or absence of an isodic(15p)(q11).
We report a patient with a 15 leads to 1 translocation who was mosaic for presence or absence of an isodic(15p)(q11). Her phenotype is similar to that of patients with deletions of proximal 15q or isodic(15p). Several phenotypes, including the Prader-Labhart-Willi syndrome, have been described with abnormalities of proximal 15q and have in common severe hypotonia, developmental delay, and lack of major congenital anomalies. Our patient is the first to be described with an isodic (15p)(q11) associated with a nonreciprocal translocation. We think her isodic(15p)(q11) arose as a result of a sister chromatid fusion rather than nonsister chromatid exchange as has been proposed in most other cases. Because of the various phenotypes described with proximal 15q abnormalities, we recommend caution in the assignment of specific phenotypes to small chromosome changes in this area.
Chromosome Banding↗
Tangier disease: heterozygote detection and linkage analysis.
A large partially inbred kindred segregating Tangier disease is analyzed for linkage to seventeen informative markers. Three criteria were developed to classify heterozygotes and each criterion's validity was subsequently evaluated by assessing the pedigree distribution of diagnoses for internal consistency. The results of the linkage analysis, while varying with the diagnostic criterion used, yield no evidence of linkage to any of the markers studied. Tight linkage (less than 5 cM) to RH, MNSS, GPT, and GLO is ruled out by all criteria.
Adult↗
Trisomy 18 mosaicism: clues to the diagnosis.
Karyotypes of blood and skin fibroblasts at ages 3 and 8.5 years had shown non-mosaic trisomy 18 in a male now of age 19. Because of his prolonged survival and an atypical phenotype, skin fibroblast cultures from a new biopsy were established at age 18, and only normal 46,XY cells were observed, while peripheral blood lymphocytes still demonstrated 47,XY, + 18. This patient and six others with trisomy 18 mosaicism illustrate the advisability of looking for such a pattern in individuals whose phenotype in early life is not fully consistent with the trisomy 18 syndrome. Additional clues to the presence of trisomy 18 mosaicism are male sex, survival beyond 2 years and lack of fingertip arches.
Adult↗
De novo interstitial deletion in the long arm of chromosome 9: a new chromosome syndrome.
An infant with an interstitial deletion 46,XY, del(9)(pter leads to q22::q32 leads to qter) is described. Clinical features included abnormal craniofacies with hypotelorism, narrow palpebral fissures, sclerocornea, deep vertical groove, and supraorbital ridge hypoplasia. There was unilateral preaxial polydactyly and toe syndactyly. Generalised hirsutism was noted. The infant had surgery for duodenal atresia but died at the age of 3 months. Unilateral renal dysplasia and accessory spleens were found at necropsy.
Abnormalities, Multiple↗
Down's syndrome phenotype and autosomal gene inactivation in a child with presumed (X;21) de novo translocation.
A 3 1/2-year-old female with clinical features of Down's syndrome was found to have extra chromosome material on the long arm of one of the X chromosomes, 46,XXq+. The parental karyotypes were normal. In the light of the clinical features of the proband an the banding characteristics of the extra chromosome material, the patient was thought to have a de novo (X;21) translocation. The results of late replication studies with BUdR and enzyme superoxide dismutase (SOD) assays in the proband suggest that: (1) the presumed (X;21) translocation chromosome was the late replicating chromosome; (2) the spread of inactivation extended from the Xq segment of the translocation chromosome to the proximal part of the segment derived from chromosome 21, leading to the inactivation of the autosomal gene for enzyme SOD; (3) the remaining distal portion of the (X;21) translocation chromosome, a part of a segment presumably derived from chromosome 21, was spared from the spread of inactivation so that this part was still genetically active and responsible for the Down's phenotype; (4) therefore, the main determinants for a Down's phenotype may be located more distally (q22.2 or q22.3 or both) than the SOD gene (q22.1) on the long arm of chromosome 21.
Bromodeoxyuridine↗
Linkage analysis of five pedigrees affected with typical autosomal dominant retinitis pigmentosa.
Five pedigrees (including an expanded version of a previously reported pedigree) exhibited typical autosomal dominant retinitis pigmentosa were analysed for linkage of RP to 29 genetic markers. No significant lod scores resulted. The largest lod score is +1.51 and suggests linkage between RP and Rh blood group at an estimated recombination fraction of 20% in males and 40% in females. Further studies are needed to confirm or refute this suggested linkage.
Adolescent↗
Possible assignment of a dominant retinitis pigmentosa gene to chromosome 1.
A genetic linkage study, performed on a large family with autosomal dominant retinitis pigmentosa (RP), demonstrated that the RP gene may be linked to the Rh locus, known to be on the short arm of human chromosome 1. Linkage studies on RP along with other studies, can help to more accurately classify these disease entities. Localizing the RP gene locus has the potential for allowing the early diagnosis of individuals at risk.
Chromosomes, Human, 1-3↗
Segregation and linkage studies of plasma dopamine-beta-hydroxylase (DBH), erythrocyte catechol-O-methyltransferase (COMT), and platelet monoamine oxidase (MAO): possible linkage between the ABO locus and a gene controlling DBH activity.
Measurements of dopamine-beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), and monoamine oxidase (MAO) along with 27 polymorphic marker phenotypes were available for 162 patients with major affective disorders and 1,125 of their relatives. Levels of enzymes were previously found not to be associated with illness. Pedigree analysis methods for quantitative traits are used to test single-gene hypotheses for segregation of DBH in 32 families with 411 individuals. COMT in 30 families with 351 individuals, and MAO in 50 families with 309 individuals. The familial distribution of both DBH and COMT are consistent with two codominant alleles at the same locus that account for 56% and 59% of the total variance, respectively. MAO activity cannot be shown to be segregating as a single major gene, but a purely nongenetic hypothesis is also rejected. A possible linkage of a locus for DBH to the ABO locus is indicated by a maximum lod score of 1.82 at 0% and 10% recombination fractions for males and females, respectively. A lod score of 0.61 at 0% recombination for a similar analysis in a single large pedigree was reported by Elston et al., making the combined lod score for the two studies equal to 2.32 at 0% recombination.
Adult↗
Familial Y-autosome translocation in two unrelated girls.
Two unrelated girls presenting with developmental delay were found to have familial Y-autosome translocations. The first had a Y;15 and the second a Y;22 translocation, involving only the Y heterochromatin on the basis of Q, C, SS, distamycin A and DAPI techniques. The first patient died of a medulloblastoma and at autopsy was found to have an adrenal neuroganglioma. The Y-autosome translocations in the affected patients were identical to those in their respective normal fathers (who had normal Y chromosomes as well). The absence of detectable translocated euchromatin from the subcentromeric region of the Y chromosome is consistent with normal female external genitalia and the absence of germ cell tumors in both patients. Whether the nongonadal neoplasias and hypoplastic uterus and ovaries in the first patient were related to the Y;15 translocation remains uncertain.
Child, Preschool↗
Genetic evidence for the inactivation of a human autosomal locus attached to an inactive X chromosome.
Mouse-human cell hybrid clones retaining an inactive translocated chromosome involving the human X and 13 were isolated. Esterase D, a marker on the segment of chromosome 13 translocated to the X, was not expressed in these clones. These results provide genetic evidence for the spreading of inactivation into the autosomal segment in an inactive human X-autosome translocation.
Animals↗
Close genetic linkage between diabetes mellitus and kidd blood group.
27 polymorphic genetic markers were analysed for possible linkage with insulin-dependent diabetes mellitus (IDDM). The data set contained 71 families with at least one affected member each. Under three different genetic models for IDDM, evidence was found for linkage between the disease and two distinct sets of marker loci: three markers on chromosome 6 (HLA, properdin factor B, and glyoxalase-1), and the Kidd blood group locus. The families apparently do not fall into two groups, one exhibiting linkage to the HLA complex and the other to the Kidd locus. Thus, two distinct disease-susceptibility loci may be involved in the inheritance of IDDM.
Blood Group Antigens↗
Familial retinoblastoma and chromosome 13 deletion transmitted via an insertional translocation.
Surviving persons from a kindred in which retinoblastoma occurred over four generations, transmitted by eight unaffected individuals, underwent chromosomal analysis. The results revealed that the development of retinoblastoma was associated with a constitutional chromosome deletion del(13)(q13.1q14.5) and that the unaffected transmitting state was associated with a balanced insertional translocation. These findings indicate that predisposition to retinoblastoma may be attributed to the loss of specific genetic material and that a chromosomal mechanism may explain apparent lack of gene penetrance in certain families. The development of unilateral, and not bilateral, retinoblastoma suggests either that the chromosome deletion is different from the mutation of heritable retinoblastoma in general, or that the chromosome deletion lessens the probability of subsequent somatic carcinogenic events.
Carboxylesterase↗
Reactivation of an inactive human X chromosome: evidence for X inactivation by DNA methylation.
A mouse-human somatic cell hybrid clone, deficient in hypoxanthine-guanine phosphoribosyltransferase (HPRT) and containing a structurally normal inactive human X chromosome, was isolated. The hybrid cells were treated with 5-azacytidine and tested for the reactivation and expression of human X-linked genes. The frequency of HPRT-positives clones after 5-azacytidine treatment was 1000-fold greater than that observed in untreated hybrid cells. Fourteen independent HPRT-positive clones were isolated and analyzed for the expression of human X markers. Isoelectric focusing showed that the HPRT expressed in these clones is human. One of the 14 clones expressed human glucose-6-phosphate dehydrogenase and another expressed human phosphoglycerate kinase. Since 5-azacytidine treatment results in hypomethylation of DNA, DNA methylation may be a mechanism of human X chromosome inactivation.
Animals↗
Ring 14 chromosome: association with seizures.
A one-year-old male with seizures and developmental delay was found to have a ring 14 chromosome without a major band deletion. This brings the number of documented r(14) cases to seven. These patients have focal cerebral atrophy with seizures as their dominant manifestation, together with few minor facial anomalies. This combination suggests that abnormalities in the 14 chromosome may result in rather nonspecific central nervous system maldevelopment and dysfunction and raises the possibility that unexplained seizures with minor anomalies and mental retardation may warrant chromosome investigation.
Chromosome Mapping↗