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L R Shapiro

Publications and source records attributed to L R Shapiro.

At least 19 recordsLinked to original sources
PubMed1995

Planning in the real world: preschool children's scripts and plans for familiar events.

3-, 4-, and 5-year-olds reported either scripts or verbal plans for 2 familiar events, going grocery shopping and going to the beach, and also constructed plans to remedy and prevent mishaps that might occur for each event. With increasing age, children reported more information, focused more on onset activities, and mentioned more specific planning activities in their plans than in their scripts. Although children at all ages provided adequate remedy plans, only 5-year-olds provided adequate prevention plans. In general, children were better at planning for the beach than for grocery shopping. Results indicate that developmental differences in event knowledge, in the ability to reflect upon event knowledge, and the event that they are planning for affect preschoolers' planning for real-world events.

Child↗
PubMed1994

Characteristics of the transmission of the FMR1 gene from carrier females in a prospective sample of conceptuses.

The Prospective Study of the Fragile X Syndrome is a large collaborative effort designed to collect prospective data on the pregnancy outcomes of individuals who carry the fragile X mutation. The goal of this 5-year study is to obtain empiric recurrence risks and population parameters for the fragile X syndrome in order to characterize the underlying mechanism of the mutation and the factors that influence its expression. This report presents the DNA results on the first 152 cases of female carriers and their pregnancy outcomes. It was found that the sex ratio of conceptuses was not significantly different from 1.0 and was not associated with mutation status. Thus, there was no evidence for selection against zygotes with full mutations. There was a significant association between the form of the mutation in carrier mothers and the frequency of its transmission. Examination of the segregation ratios from premutation mothers showed that there was a deficit of conceptuses that received the fragile X mutation. The segregation ratio from full mutation carrier mothers did not differ from expected. Several explanations for this observation are discussed. Numbers of cases are too small to estimate recurrence risks; however, the general trend of the data confirm the association of recurrence risks and the repeat number carried by the mother.

Female↗
PubMed1994

Asymmetry of methylation with FMR-1 full mutation in two 45,X/46,XX mosaic females associated with normal intellect.

The full FMR-1 mutation is known to cause the fragile X syndrome [Fra(X)], but variable expression in females, including normal to deficient intellect, may be related to random X-inactivation (lyonization). We have evaluated 2 mosaic 45,X/46,XX females who are cytogenetically fra(X) positive, have an FMR-1 full mutation, and are of normal intellect. There were 50% fra(X) chromosomes in the 45,X cells of one of the females; this has not been reported previously. In both patients, there was a strong asymmetry of FMR-1 methylation with the normal allele being totally or 90% unmethylated and the mutant allele being similarly methylated. Thus, the apparent selective inactivation of the full mutant FMR-1 allele appears to have resulted in limited expression with normal intellect. The presence of the fra(X) chromosome in 45,X cells is unique; however, there may be no relationship to the asymmetric inactivation of the mutant allele which could be due to chance or a mechanism yet to be delineated.

Adolescent↗
PubMed1993

Multiple meningiomas in a patient with constitutional ring chromosome 22.

We report on a patient with multiple congenital anomalies and ring chromosome 22 who died at age 16 years of bronchopneumonia. Autopsy documented multiple psammomatous meningiomas of the spinal dura and tentorium. Tumor tissue for cytogenetic analysis was not available. Although abnormalities of chromosome 22 in tumor tissue have been reported, to our knowledge, this is only the third report of a constitutional chromosome 22 abnormality associated with the development of meningiomas. Thus, a constitutional chromosome 22 abnormality may predispose to the development of meningiomas.

Abnormalities, Multiple↗
PubMed1993

Interrelationships of the hemifacial microsomia-VATER, VATER, and sirenomelia phenotypes.

The phenotypes of hemifacial microsomia-VATER, VATER, and sirenomelia patients suggest a sequence of overlapping developmental abnormalities. The malformations of 247 hemifacial microsomia (HFM) patients with one or more anomalies in other body regions were analyzed and compared with those of 255 VATER and 101 sirenomelia patients studied in the same fashion. The HFM patients were analyzed in four subgroups delineated by the number of their concomitant VATER ascertainment abnormalities (VAA). Three or more VAA occurred in 33 HFM patients who were designated to have the HFM-VATER phenotype and while no significant alteration of the HFM phenotype was found, there were notable differences in the analyses of the 20 malformation categories studied. Analyzed in separate heart and blood vessel (BV) categories, occurrences of BV defects in HFM patients with 0-1 VAA were low (4-6%) and due to anomalies other than single umbilical arteries (SUA). The BV abnormalities increased to 20% in the HFM with two VAA, HFM-VATER, and VATER phenotypes with equal occurrences of SUA and other BV anomalies. The incidence of SUA was markedly increased (64%) in the sirenomelia. Heart defects rose from 22% to 40% with the increasing VAA in individual HFM patients but were less in VATER (29%) and sirenomelia (21%) patients and were attributed to complex, conotruncal, and other early embryonic anomalies. Unilateral agenesis of paired organs systems occurred frequently and, possibly, can be attributed to an absent blood supply. Each phenotype of the sequence also had increased VAA, rib/vertebrae hypersegmentation, and monozygotic twinning. The variation in the incidences of malformations in the three phenotypes can be attributed to their relative location in the craniocranial organogenesis sequence of normal human embryologic development.

Abnormalities, Multiple↗
PubMed1993

Kallmann syndrome associated with complex chromosome rearrangement.

We report on a male with Kallmann syndrome (KS) and an apparently balanced complex chromosome rearrangement (CCR): 46,XY,t(3; 9)(9;12)(q13.2;q21.2p13;q15). This is the first known report of a CCR in the KS and the second reported case of a definitive autosomal chromosome abnormality with KS. Possible relationships between the cytogenetic abnormality and KS are discussed.

Adult↗
PubMed1993

Longitudinal comparison of temporal-modulation perimetry with white-on-white and blue-on-yellow perimetry in ocular hypertension and early glaucoma.

We obtained data over 3 years on temporal-modulation perimetry (TMP), standard automated [white-on-white (W/W)] perimetry, and short-wavelength-sensitive [blue-on-yellow (B/Y)] perimetry in ocular hypertensive (OH) patients and patients with early glaucomatous visual-field loss (EG). Evidence of visual-field defects was obtained with the use of both B/Y perimetry and TMP in the majority of OH and EG eyes that demonstrated progression on W/W perimetry as well as in all stable EG eyes. Using the nerve-fiber-bundle pattern to compare testing procedures, we determined that these defects were generally as extensive or more extensive than the concurrent W/W abnormalities. In terms of location over the 3 years of testing, TMP and B/Y defects were reasonably consistent in the EG eyes, somewhat less consistent in the OH eyes demonstrating progression, and both inconsistent and infrequent in the stable OH eyes. The greatest degree of overlap occurred between the location of defects obtained by use of the higher TMP frequencies (8 and 16 Hz) and that of defects obtained by use of B/Y perimetry. Since these two methods are thought to isolate different visual mechanisms subserved by different visual pathways, these results suggest that early glaucomatous visual-field damage as revealed by TMP and B/Y perimetry may not be specific to a single visual pathway.

Color Perception Tests↗
PubMed1992

Proposed guidelines for diagnosis of chromosome mosaicism in amniocytes based on data derived from chromosome mosaicism and pseudomosaicism studies.

Currently, accepted protocol which has been developed at the Prenatal Diagnosis Laboratory of New York City (PDL) requires that when a chromosome abnormality is found in one or more cells in one flask, another 20-40 cells must be examined from one or two additional flasks. Chromosome mosaicism is diagnosed only when an identical abnormality is detected in cells from two or more flasks. In a recent PDL series of 12,000 cases studied according to this protocol, we diagnosed 801 cases (6.68 per cent) of single-cell pseudomosaicism (SCPM), 126 cases (1.05 per cent) of multiple-cell pseudomosaicism (MCPM), and 24 cases (0.2 per cent) of true mosaicism. Pseudomosaicism (PM) involving a structural abnormality was a frequent finding (2/3 of SCPM and 3/5 of MCPM), with an unbalanced structural abnormality in 55 per cent of SCPM and 24 per cent of MCPM. We also reviewed all true mosaic cases (a total of 50) diagnosed in the first 22,000 PDL cases. Of these 50 cases, 23 were sex chromosome mosaics and 27 had autosomal mosaicism; 48 cases had numerical abnormalities and two had structural abnormalities. Twenty-five cases of mosaicism were diagnosed in the first 20 cells from two flasks, i.e., without additional work-up, whereas the other 25 cases required extensive work-up to establish a diagnosis (12 needed additional cell counts from the initial two culture flasks; 13 required harvesting a third flask for cell analysis). Our data plus review of other available data led us to conclude that rigorous efforts to diagnose true mosaicism have little impact in many instances, and therefore are not cost-effective. On the basis of all available data, a work-up for potential mosaicism involving a sex chromosome aneuploidy or structural abnormality should have less priority than a work-up for a common viable autosomal trisomy. We recommend revised guidelines for dealing with (1) a numerical versus a structural abnormality and (2) an autosomal versus a sex chromosome numerical aneuploidy. Emphasis should be placed on autosomes known to be associated with phenotypic abnormalities. These new guidelines, which cover both flask and in situ methods, should result in more effective prenatal cytogenetic diagnosis and reduced patient anxiety.

Amniocentesis↗
PubMed1992

Properties of staircase procedures for estimating thresholds in automated perimetry.

The properties of the staircase procedure as applied in automated perimetry were examined. Two computer simulation models were used to vary different test- and patient-related parameters in clinical perimetry. One model was based on the KRAKEN computer simulation program; the other computer simulation was based on stimulus-response data sets from 11 normal subjects. The results were analyzed in terms of efficiency and accuracy. It was found that: (1) in general, there was an efficiency-accuracy trade-off; (2) increases in response fluctuation produced substantially greater errors in threshold estimates; (3) little or no improvements in accuracy were achieved by increasing the number of reversals; (4) the starting position of the staircase relative to the threshold influenced the efficiency of threshold determinations but not their accuracy; (5) a single-response error reduced the efficiency of staircases; (6) the position of a single-response error in a staircase sequence influenced the accuracy and efficiency of the threshold determination; and (7) more than one response error during a staircase sequence always resulted in a marked reduction in accuracy and/or efficiency. Current perimetric strategies appear to be at or near optimal levels, and therefore, strategies in the future may need to depart from a staircase-style procedure to achieve a significant increase in both accuracy and efficiency. Computer simulation studies can provide an effective means of evaluating perimetric test procedures and defining optimum strategies, which then can be verified clinically by subsequent testing in patient populations.

Adolescent↗
PubMed1991

Sacrococcygeal dysgenesis association.

In the malformation analysis of 445 patients ascertained only for a sacrococcygeal malformation, a new phenotype, the sacrococcygeal dysgenesis association (SDA), was delineated in 34%. In addition, sirenomelia patients were found in 12%, the VATER association in 27%, and 27% could not be classified. Heterogeneity in the patients with sacrococcygeal malformations was identified by the differences found in their associated malformations. SDA patients have a relatively small average number (3.3) of anomalies per patient as compared with 9.3 in sirenomelia and 6.2 in VATER patients. SDA abnormalities occurred to a significant degree only in 6 of 20 designated malformation categories (vertebral, rib, pelvic, lower limb, central nervous system [CNS], renal) in contrast to 17 in VATER and 18 in sirenomelia patients. The SDA vertebral malformation pattern also differed from that of VATER/sirenomelia patients as did the high sacrococcygeal agenesis:dysgenesis ratio and low thoracolumbar vertebrae and/or rib hypersegmentations. Most significantly, SDA patients had a large number of CNS anomalies and CNS-related dysfunctions of the urinary and distal intestinal tracts but no anatomic urinary or intestinal tract malformations. This contrasted sharply with the markedly increased occurrences of anatomic abnormalities in these body regions of the sirenomelia and VATER patients. Demographic data such as patient survival, twinning and, particularly, the high (28%) incidence of maternal diabetes in the SDA further support its differentiation from VATER/sirenomelia patients.

Abnormalities, Multiple↗
PubMed1991

Prader-Willi syndrome and Robertsonian translocations involving chromosome 15.

A case of Prader-Willi syndrome is presented in which high resolution chromosome analysis revealed not only a familial Robertsonian translocation [t(13q15q)], but also a del(15) (q11.2q13) of the chromosome 15 not involved in the translocation. While there have been numerous reports of Robertsonian translocations involving chromosome 15 in patients with Prader-Willi syndrome, in this case, the Robertsonian translocation was shown to be unrelated to the clinical findings.

Adult↗
PubMed1991

Molecular markers of fragile X: clinical aspects of carrier detection and prenatal diagnosis.

In our families, a determination of carrier or affected status was made in more than 75% of cases using a standard panel of five marker systems: three proximal (F9, DXS105, DXS98) and two distal (F8, DXS52). Five additional systems, three proximal (DXS10, DXS51, DXS102) and two distal (DXS15, DXS33), were used in cases resistant to analysis with the standard panel. In 60% of cases, flanking markers were identified (proximal and distal). Utilizing the complete panel, only 5% of cases did not have any informative markers identified. In order to facilitate the appropriate application of molecular methods, several simple rules should be followed by the genetic service provider when dealing with fra(X) families: 1. Cytogenetic prescreening of females may be helpful. Only negative or ambiguous fra(X) expression levels justify the labor-intensive DNA-based family studies. 2. At present, DNA-based studies are the only way to ascertain male carrier status. 3. Every effort should be made to perform DNA-based studies under maternal phase-known conditions. 4. Information should be collected and pedigrees prepared for both sets of maternal grandparents. 5. Fathers of female consultands should be directly DNA-typed to rule out non-paternity. 6. Genetic counseling should be conservative, i.e. the "worst" scenario presented to these families, in order to avoid underestimating the risk of transmission to the next generation.

Cells, Cultured↗
PubMed1991

The fragile X syndrome--clinical overview.

The Fra(X) syndrome is the most common inherited cause of mental retardation. It is associated with an unusual form of X-linked inheritance where both men and women can be carriers. The "X-inactivation imprinting model" proposed by Laird et al currently offers one explanation of the unusual genetics. Recognition of clinical features and accurate cytogenetic diagnosis is important because of the prevalence of this disorder and the necessity and demand for genetic counseling. A combination of fra(X) cytogenetic studies and DNA-based linkage analysis for carrier detection and prenatal diagnosis is currently in use and is undergoing development and improvement.

Chromosome Fragility↗