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K Devriendt

Publications and source records attributed to K Devriendt.

At least 145 records · Page 8Linked to original sources
PubMed1997

Regional localization of two genes for nonspecific X-linked mental retardation to Xp22.3-p22.2 (MRX49) and Xp11.3-p11.21 (MRX50).

Two families with nonspecific X-linked mental retardation (XLMR) are presented. In the first family, MRX49, 5 male patients in 2 generations showed mild to moderate mental retardation. Two-point linkage analysis with 28 polymorphic markers, dispersed over the X-chromosome, yielded a maximal LOD score of 2.107 with markers DXS7107 and DXS8051 at theta = 0.0, localizing the MRX49 gene at Xp22.3-p22.2, between Xpter and marker DXS8022. Multipoint linkage analysis showed negative LOD values over all other regions of the chromosome. In the second family, MRX50, 4 males in 2 generations showed moderate mental retardation. Pairwise linkage analysis with 28 polymorphic markers yielded a LOD score of 2.056 with markers DXS8054, DXS1055, and DXS1204, all at theta = 0.0. Flanking markers were DXS8012 and DXS991, situating the MRX50 gene at Xp11.3-Xp11.21, in the pericentromeric part of the short arm of the X chromosome.

Adolescent↗
PubMed1997

A recognisable behavioural phenotype associated with terminal deletions of the short arm of chromosome 8.

We report the clinical findings in 5 patients with a terminal deletion of the short arm of chromosome 8. Mild developmental delay was constantly present, in association with microcephaly in 4 of 5 patients. Facial anomalies were mild or absent. A congenital heart defect was present in 3 patients: an atrioventricular septal defect (AVSD) in 2 and an atrial septal defect type II (ASDII) with pulmonary stenosis in one. A highly similar pattern of behavioural difficulties was present in the 3 older children (8-11 years), with outbursts of aggressiveness and destructive behaviour. Follow-up in one patient showed that at the age of 16 years, these behavioural problems had largely disappeared. This observation suggests that in addition to mental retardation, microcephaly, congenital heart defect (typically AVSD), a terminal deletion of chromosome 8p may be associated with a characteristic behavioural phenotype during childhood.

Behavioral Symptoms↗
PubMed1997

The X-linked infantile spasms syndrome (MIM 308350) maps to Xp11.4-Xpter in two pedigrees.

We report 2 families with X-linked infantile spasms syndrome (X-linked West syndrome). Data from clinical examination, biochemical analysis, neuroimaging, and neuropathology are discussed. In these families, genetic linkage analysis was able to locate the disease gene to the distal part of the short arm of the X chromosome, between Xpter and Xp11.4. This is the first report of linkage with genetic markers in this disorder. Although most cases are sporadic, further unraveling of the genetic background of the familial cases might greatly improve our understanding of infantile spasms.

Child, Preschool↗
PubMed1997

Interstitial telomeric sequences at the junction site of a jumping translocation.

The mechanism(s) for the origin of jumping translocations (JTs) are unknown. To assess the possible involvement of telomeric sequences in the jumping process, metaphases of a patient with hydrops fetalis having a JT were analyzed for the presence of interstitial telomeres. Telomere DNA sequences were detected at the junction sites of the donor and the recipient chromosomes. Interstitial telomeric sequences have so far only been detected in JTs involving chromosome 15q in patients with Prader-Willi syndrome. Our finding of interstitial telomeric sequences in a JT with a chromosome different from chromosome arm 15q in a patient without Prader-Willi syndrome implies that telomere sequences may be common to all telomeric JTs. The possible role of telomeric sequences as a cause of the observed chromosomal mosaicism is discussed.

Chromosomes, Human, Pair 4↗
PubMed1997

Submicroscopic deletion in chromosome 22q11 in trizygous triplet siblings and their father. Clinical variability of 22q11 deletion.

A submicroscopic deletion of chromosome 22q11 was demonstrated in three triplets and in their father. Two children had the typical DiGeorge sequence with at least three of the four cardinal features: conotruncal heart disease, hypoplastic thymus and typical facial features. Hypoparathyroidism was present in one of them. The third child had features of both DiGeorge and velo-cardio-facial syndrome (VCFS). The father presented with features compatible with VCFS. This observation further illustrates the wide variability in expression of a submicroscopic deletion of 22q11, even within one family.

Abnormalities, Multiple↗
PubMed1997

X-linked severe mental retardation and a progressive neurological disorder in a Belgian family: clinical and genetic studies.

The combination of X-linked mental retardation (XLMR) and neurological disorders occurs in a number of syndromes. Differential diagnosis mostly depends on clinical data and mapping of responsible genes by linkage analysis. We present a Belgian family with severe XLMR and a progressive neurological disorder with ataxia, spasticity and convulsions. Biochemical investigations, neuroimaging and neuropathology were normal. Linkage analysis pointed to region Xq27-28 as the probable locus for the genetic defect. The sequence of the L1CAM cDNA, a possible candidate gene, proved to be normal in the patients. This suggests the presence of a genetic factor on Xq27-28, different from L1CAM, which can lead to severe XLMR and a progressive neurological 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

Trisomy 15 rescue with jumping translocation of distal 15q in Prader-Willi syndrome.

We report a patient with Prader-Willi syndrome (PWS) and mosaicism for a de novo jumping translocation of distal chromosome 15q, resulting in partial trisomy for 15q24-qter. A maternal uniparental heterodisomy for chromosome 15 was present in all cells, defining the molecular basis for the PWS in this patient. The translocated distal 15q fragment was of paternal origin and was present as a jumping translocation, involving three different translocation partners, chromosomes 14q, 4q, and 16p. The recipient chromosomes appeared cytogenetically intact and interstitial telomere DNA sequences were present at the breakpoint junctions. This strongly suggests that the initial event leading to the translocation of distal 15q was a non-reciprocal translocation, with fusion between the 15q24 break-point and the telomeres of the recipient chromosomes. These observations are best explained by a partial zygotic trisomy rescue and comprise a previously undescribed mechanism leading to partial trisomy.

Adult↗
PubMed1997

Chromosome 22q11 deletion presenting as the Potter sequence.

A female fetus with the Potter sequence, caused by unilateral renal agenesis and contralateral multicystic renal dysplasia, was found to have a submicroscopic deletion in chromosome 22q11. The only associated anomaly was agenesis of the uterus and oviducts (Von Mayer-Rokitansky-Küster anomaly). The deletion was inherited from the father, who presented the typical velocardiofacial syndrome phenotype, but no urological anomalies. This observation further extends the clinical spectrum associated with a deletion in 22q11.

Abnormalities, Multiple↗
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

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↗
PubMed1997

Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations.

Renal-coloboma syndrome is a recently described autosomal dominant syndrome of abnormal optic nerve and renal development. Two families have been reported with renal-coloboma syndrome and mutations of the PAX2 gene. The PAX2 gene, which encodes a DNA-binding protein, is expressed in the developing ear, CNS, eye, and urogenital tract. Ocular and/or renal abnormalities have been consistently noted in the five reports of patients with renal-coloboma syndrome, to date, but PAX2 expression patterns suggest that auditory and CNS abnormalities may be additional features of renal-coloboma syndrome. To determine whether additional clinical features are associated with PAX2 mutations, we have used PCR-SSCP to identify PAX2 gene mutations in patients. We report here four patients with mutations in exon 2, one of whom has severe ocular and renal disease, microcephaly, and retardation, and another who has ocular and renal disease with high-frequency hearing loss. Unexpectedly, extreme variability in clinical presentation was observed between a mother, her son, and an unrelated patient, all of whom had the same PAX2 mutation as previously described in two siblings with renal-coloboma syndrome. These results suggest that a sequence of seven Gs in PAX2 exon 2 may be particularly prone to mutation.

Abnormalities, Multiple↗
PubMed1997

DiGeorge syndrome and unilateral symbrachydactyly.

We describe a child with DiGeorge syndrome due to a del22(q11) and a symbrachydactyly of the left hand. The underlying cardiovascular malformations in DiGeorge syndrome may lead to an increased susceptibility to vascular disruptions, giving further support to the subclavian-artery-disruption-sequence theory.

Arm↗
PubMed1996

Structure, sequence, and chromosome 19 localization of human USF2 and its rearrangement in a patient with multicystic renal dysplasia.

The precise etiology of hydronephrosis caused by pelvi-ureteric junction obstruction is not yet known but there is convincing evidence for a genetic cause, with linkage analysis predicting a hereditary hydronephrosis locus on chromosome 6p. In previous studies, a patient was described with a de novo autosomal t(6;19)(p21;q13.1) translocation and suffering from bilateral multicystic renal dysplasia (MRD) caused by a bilateral complete pelvi-ureteric junction obstruction. In an effort to elucidate a possible correlation between this translocation and hereditary hydronephrosis, we have carried out an extensive molecular characterization of a chromosome 19 cosmid clone previously identified as spanning the translocation in this unique index case. DNA sequencing across a 9.2-kb BamHI fragment that straddles the translocation indicates the presence of DNA sequences with a high degree of similarity to the USF2 gene that encodes the transcription factor USF2 (upstream stimulator factor 2). The genomic structure of USF2 consists of 10 exons distributed over a DNA region of about 11 kb. The putative promoter region is GC-rich and lacks TATA and CCAAT boxes, suggesting that expression of the USF2 gene may be controlled by a typical housekeeping gene promoter. The chromosome 19 breakpoint in the MRD patient appeared to have occurred in intron 7 of the USF2 gene. Northern blot analysis of a variety of human tissues revealed that the USF2 gene is ubiquitously expressed. Furthermore, Northern blot and 3'-RACE analysis of mRNA isolated from lung fibroblasts of the MRD patient failed to detect a fusion transcript involving USF2 sequences, suggesting gene disruption rather than the generation of a fusion gene as a possible underlying mechanism.

Amino Acid Sequence↗