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Biomedical subjects

E Legius

Publications and source records attributed to E Legius.

At least 73 records · Page 4Linked to original sources
PubMed1998

The macrocephaly-cutis marmorata telangiectatica congenita syndrome. Long-term follow-up data in 4 children and adolescents.

We present the clinical history and findings in 4 children and adolescents with the association of macrocephaly and cutis marmorata telangiectatica congenita (Macrocephaly-CMTC syndrome). This syndrome has recently been delineated within the general group of patients with manifestations of cutis marmorata telangiectatica-Klippel-Trenaunay-Weber syndrome as a clinically recognisable entity.

Adolescent↗
PubMed1997

Increased proportion of exon 9 alternatively spliced CFTR transcripts in vas deferens compared with nasal epithelial cells.

CFTR transcripts have been qualitatively and quantitatively analysed in nasal epithelial and vas deferens cells by means of reverse transcription PCR. Alternative splicing of exon 9, which is known to occur in nasal epithelial cells, also occurred in vas deferens cells. The extent of this alternative splicing was determined by the allele present at the Tn locus at the end of intron 8 of the CFTR gene. However, the proportion of transcripts lacking exon 9 sequences was increased in vas deferens cells compared with nasal epithelial cells, independent of the Tn genotype. We postulate that this tissue specific difference in the proportion of CFTR transcripts lacking exon 9 sequences could contribute to the tissue specific disease phenotype observed in individuals with congenital bilateral absence of the vas deferens.

Alternative Splicing↗
PubMed1997

A study of the cognitive and psychological profile in 16 children with congenital or juvenile myotonic dystrophy.

We report data on intelligence and on possibly associated psychopathology in 16 children and adolescents, between 7 and 18 years of age, with congenital or juvenile myotonic dystrophy. We found that all the subjects have an intelligence level below the population mean, four of them in the mentally retarded range. An unexpected number of subjects are in the clinical range on the Child Behavior Checklist. In nine of the 16 subjects, a child psychiatric diagnosis was found using a standardized psychiatric interview. The most frequent child psychiatric diagnosis was Attention Deficit Hyperactivity Disorder.

Adolescent↗
PubMed1997

Prader-Willi syndrome in a child with mosaic trisomy 15 and mosaic triplo-X: a molecular analysis.

A 3.3 year old girl with Prader-Willi syndrome (PWS) and mosaicism for two aneuploidies, 47,XXX and 47,XX,+15, is presented. The triplo-X cell line was found in white blood cells and fibroblasts, the trisomy 15 cell line in 50% of the fibroblasts. Using methylation studies of the PWS critical region and by polymorphic microsatellite analysis, the existence of uniparental maternal heterodisomy for chromosome 15 was shown in white blood cells. This provided a molecular explanation for the PWS in this child. In fibrolasts, an additional paternal allele was detected for markers on chromosome 15, which is in agreement with the presence of mosaicism for trisomy 15 in these cells. This example provides direct evidence for trisomic rescue by reduction to disomy as a possible basis for PWS. Whereas the trisomy 15 was caused by a maternal meiosis I error, the triplo-X resulted from a postzygotic gain of a maternal X chromosome, as shown by the finding of two identical maternal X chromosomes in the 47,XXX cell line. Because the triplo-X and the trisomy 15 were present in different cell lines, gain of an X chromosome occurred either in the same cell division as the trisomy 15 rescue or shortly before or after.

Alleles↗
PubMed1997

Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of 37 children and adolescents with VCFS.

We report data on a group of 37 VCFS patients with specific reference to their intelligence, behaviour, and social competence. Fifty five percent of the children had a borderline to normal IQ. Mental retardation (defined as IQ < 70 or > -2 SD below the mean) was found in 45%. In the majority, the mental retardation was mild (38%) and only two patients had moderate mental retardation. Severe mental retardation seems to be rare in VCFS. The present study shows also that the incidence of mental retardation is much higher in the familial than the de novo group. Intelligence is not correlated with the presence or absence of a heart defect. Significantly higher verbal IQs than performance IQs (probably related to deficits in visuospatial-perceptual functioning) were found. Problems in social-emotional functioning and attention were also found. Further longitudinal studies are necessary to provide an accurate prognosis and appropriate intervention for VCFS children.

Abnormalities, Multiple↗
PubMed1997

Gender-specific regional changes in genetic structure of muscularity in early adolescence.

Genetic and environmental influences on muscle circumference measurements of the extremities were estimated in 105 pairs of twins between 10 and 14 yr of age. Four circumferences, extended upper arm (EAC), forearm (FC), thigh (TC), and calf (CC), were measured. Univariate model fitting revealed that the largest part (87-95%) of the variance for all circumferences at most ages was explained by additive genetic factors. Sex differences were observed for some age categories. Multivariate analyses showed a different pattern evolving according to age and gender. In boys from 10 to 12 yr of age, one general genetic factor influenced all four circumferences. With increasing age, an arm-leg model emerged, one genetic factor influencing the arm and another genetic factor the leg circumferences. In young girls one genetic factor loaded on the proximal (EAC, TC) and another on the distal (FC, CC) circumferences. With subjects at age 14 yr, an arm-leg model was observed. High genetic correlations indicated that genetic factors related to EAC, FC, TC, and CC did not act independently. The age-and gender-specific changes in the genetic structure suggest pubertal influences. This study shows that muscle circumferences are highly heritable characteristics and are therefore a promising starting point at which to locate their genes. Gene mapping could validate the gender-specific change of the genetic structure with age and region.

Adolescent↗
PubMed1997

Skewed X-chromosome inactivation in female carriers of dyskeratosis congenita.

In this study, we report on a family with X-linked dyskeratosis congenita (DC). Linkage analysis with markers in the factor VIII gene at Xq28 yielded a LOD score of 2 at a recombination of 0. Clinical manifestations of DC, such as skin lesions following the Blaschko lines, were present in two obligate carrier females. Highly skewed X inactivation was observed in white blood cells, cultured skin fibroblasts, and buccal mucosa from female carriers of DC in this family. This suggests a critical role for the DC gene in bone marrow-cell and fibroblast-cell proliferation.

Adult↗
PubMed1996

Molecular-intelligence correlations in young fragile X males with a mild CGG repeat expansion in the FMR1 gene.

Several mechanisms can explain the occurrence of full-mutation fragile X males with an IQ level above -2 SD below mean, also called "high-functioning fragile X males." Incomplete methylation of the CpG island at the 5' end of the FMR1 gene is one of these mechanisms. The present study describes the physical and behavior phenotypes in 7 fragile X boys with CGG repeat insertions in the FMR1 gene between 600-2,400 base pairs. The degree of methylation at the FMR1-associated CpG island ranges in peripheral blood lymphocytes from 0-95%. Subjects with a low degree of methylation at this site have mild or absent physical characteristics of the fragile X syndrome, while subjects with a high degree of methylation at this site have more severe physical characteristics. In this range of CGG repeat insertion (600-2,400 base pairs), the degree of methylation at the FMR1-associated CpG island is a good predictor of intelligence, while CGG repeat insertion length is not.

Adolescent↗
PubMed1996

New findings in the behavioral profile of young FraX females.

Nine girls, with a 50% risk to be carrier of the FMR-1 gene and who attended normal school and did not have a mentally retarded fraX relative, were selected to exclude influences of external factors. These subjects were submitted to an extensive neurocognitive and psychiatric evaluation before molecular analysis of their FMR-1 status was done to obtain completely unbiased results. The findings of this study suggest that differentiation according to the FMR-1 status may be more significant at the neurocognitive level than at the behavioral level and support the hypothesis that behavioral problems are more influenced by external factors than by the FMR-1 carrier state.

Adolescent↗
PubMed1996

Evidence for genetic heterogeneity in the carbohydrate-deficient glycoprotein syndrome type I (CDG1).

We have analyzed a series of polymorphic markers on chromosome 16p13 in 17 families with carbohydrate-deficient glycoprotein syndrome type I (CDG1). First, linkage to the region between D16S406 and D16S500 is confirmed. The telomeric border of the candidate region is now definitively placed proximal to D16S406 by crossovers observed in 2 families. Second, in 1 family with 2 affected siblings, the disease is not linked to chromosome 16p. Genetic heterogeneity has not been previously reported for CDG1, and this observation has implications for prenatal diagnosis. Third, allelic associations suggest that the disease locus is localized close to D16S414/D16S497. This places the region of interest centromeric of its published localization.

Chromosomes, Human, Pair 16↗
PubMed1996

Linkage analysis in three families with nonspecific X-linked mental retardation.

Nonspecific X-linked mental retardation (XLMR) is a common disorder. The number of genes involved in this condition is not known, but it is estimated to be more than 10. We present a clinical and linkage study on 3 families with XLMR. All families were analyzed using highly polymorphic markers covering the X chromosome; screening for the fragile X mutation was negative. The first family (MRX 36) consisted of 1 female and 4 male patients in 3 generations and 7 healthy individuals. Considering the female as an expressing heterozygous carrier, a maximum LOD score of 3.41 was reached in region Xp21.2-Xp22.1. Considering her phenotype to be unknown, a LODmax of 1.97 was reached in the same region. The second family consisted of 5 affected and 6 healthy males with mild to borderline mental retardation. Linkage analysis using an X-linked recessive model with full penetrance and no phenocopies excluded linkage over almost the entire X chromosome. Using alternative models, including an affecteds-only analysis, a LODmax of 1.49 was found in region Xq24-28. The third family, consisting of 4 male patients with moderate mental retardation in 1 generation yielded a LODmax of 0.9 in region Xp22.13-11.3. However, even in this small pedigree, exclusion mapping was able to exclude very large parts of the X chromosome and in this way identify a likely candidate region.

Child, Preschool↗
PubMed1996

Neurofibromatosis type I gene mutation in a patient with features of LEOPARD syndrome.

Multiple lentigines (LEOPARD) syndrome has been delineated as an autosomal dominant disorder with lentigines, cardiac abnormalities, variable mental retardation, and typical craniofacial features as the most characteristic findings. LEOPARD syndrome shows a great clinical overlap with neurofibromatosis type 1 (NF1). In this report we describe a de novo missense mutation (M 1035R) in exon 18 of the NF1 gene in a young woman with a prior diagnosis of LEOPARD syndrome. We hypothesize that some patients now diagnosed with LEOPARD syndrome have in fact a mutation in the NF1 gene, whereas in other patients with LEOPARD syndrome, a different gene might be involved.

Abnormalities, Multiple↗
PubMed1996

Congenital scalp defect, distal limb reduction anomalies, right spastic hemiplegia and hypoplasia of the left arteria cerebri media. Further evidence that interruption of early embryonic blood supply may result in Adams-Oliver (plus) syndrome.

In this report we describe a male patient with the interesting combination of a large congenital scalp defect, distal limb reduction anomalies, right spastic hemiplegia and hypoplasia of the left arteria cerebri media. Follow-up data from birth up to the age of 18 years revealed positive evolution with low to normal intelligence. The findings in the present patient, i.e. an Adams-Oliver syndrome associated with a severe neurological deficit, are best explained as resulting from interruption of the early embryonic blood supply.

Abnormalities, Multiple↗
PubMed1996

De novo 46,XX, dir dup (11)(q133.3-->q14.2) in a patient with mental retardation, congenital cardiopathy and thrombopenia.

A 31-year-old female is reported with mild to moderate mental retardation, facial dysmorphy, congenital cardiopathy, and mild thrombocytopenia as the most important clinical findings. Chromosome analysis in lymphocytes showed a de novo dir dup (11)(q13.3-->14.2), by both G-banding and FISH techniques. Previously reported constitutional duplications of 11q are mostly the result of unbalanced translocations involving chromosome 11q, and are associated with a partial monosomy or trisomy of the translocation partner chromosome. In case of an unbalanced translocation it is not clear which clinical findings result from the chromosome 11 duplication and which result from the abnormality on the translocation partner chromosome. This is the first report on a constitutional duplication of chromosome region 11q13.3-->14.2 without involvement of other chromosomes.

Adult↗