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K Devriendt

Publications and source records attributed to K Devriendt.

At least 73 records · Page 4Linked to original sources
PubMed2001

Clinical features in 130 patients with the velo-cardio-facial syndrome. The Leuven experience.

The velo-cardio-facial syndrome (VCFS) is a leading cause of velopharyngeal dysfunction and cleft palate and caused by a submicroscopic deletion in the long arm of chromosome 22 (band 22q11). During the last 5 years, 130 patients with a 22q11 deletion were diagnosed in Leuven. Most patients presented a wide variety of the classical features of the velo-cardio-facial syndrome. Velopharyngeal dysfunction was almost always present whereas an isolated cleft lip/palate was observed in a minority of patients. The velopharyngeal function can be evaluated by the classic combination of indirect and direct techniques. Because of the frequent occurrence of the velo-cardio-facial syndrome, estimated at around 1/4000 live births, and given the extremely broad clinical spectrum which makes clinical diagnosis difficult, screening of patients with velopharyngeal dysfunction for a deletion 22q11 is indicated.

Abnormalities, Multiple↗
PubMed2001

Children with a 22q11 deletion versus children with a speech-language impairment and learning disability: behavior during primary school age.

Children with a 22q11 deletion versus children with a speech-language impairment and learning disability: behavior during primary school age: Common behavioral features described in children with the Velo-Cardio-Facial syndrome (VCFS) (del 22q11) are problems with attention and concentration, extremes in behavior and social problems, especially in relationship with peers. At present, it is unclear whether these behavioral manifestations are directly related to the chromosomal anomaly or related to other manifestations of the syndrome such as developmental delay and speech-language delay. This study describes for the first time the behavior of young primary school aged children with a del22q11 compared to a control group of children matched for age, sex and mental level, with similar developmental problems (speech-language impairment plus learning disability: SLI + LD) but without a del22q11 or any other known genetic condition. Parents and teachers evaluated the children's behavior with standardized questionnaires (CBCL; TRF). Results indicate that most of the behaviors are similar across both groups. The only differences found are in the field of < > and < >. Children with a del22q11 have a stronger tendency to withdraw from others, whereas children with a SLI+LD seem to be more aggressive.

Abnormalities, Multiple↗
PubMed2000

Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III.

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.

Adolescent↗
PubMed2000

Novel syndromic form of X-linked complicated spastic paraplegia.

This study presents a family with a syndromic form of X-linked mental retardation in which four males in two generations present severe mental retardation, slowly progressive spastic paraplegia, facial hypotonia, and maxillary hypoplasia. Multipoint linkage analysis with 24 highly polymorphic markers indicated two possible candidate regions: Xp21.1-Xq21.3 (flanking markers DXS1214 and DXS990) and Xq23-Xq27.1 (flanking markers DXS8020 and DXS984). The two known loci for X-linked mental retardation and spastic paraplegia are excluded: proteolipid protein in Xp21 and L1 cell adhesion molecule in Xq28. Therefore, the syndrome in this family appears to represent a previously undescribed X-linked spastic paraplegia-mental retardation syndrome.

Adolescent↗
PubMed2000

GATA3 haplo-insufficiency causes human HDR syndrome.

Terminal deletions of chromosome 10p result in a DiGeorge-like phenotype that includes hypoparathyroidism, heart defects, immune deficiency, deafness and renal malformations. Studies in patients with 10p deletions have defined two non-overlapping regions that contribute to this complex phenotype. These are the DiGeorge critical region II (refs 1, 2), which is located on 10p13-14, and the region for the hypoparathyroidism, sensorineural deafness, renal anomaly (HDR) syndrome (Mendelian Inheritance in Man number 146255), which is located more telomeric (10p14-10pter). We have performed deletion-mapping studies in two HDR patients, and here we define a critical 200-kilobase region which contains the GATA3 gene. This gene belongs to a family of zinc-finger transcription factors that are involved in vertebrate embryonic development. Investigation for GATA3 mutations in three other HDR probands identified one nonsense mutation and two intragenic deletions that predicted a loss of function, as confirmed by absence of DNA binding by the mutant GATA3 protein. These results show that GATA3 is essential in the embryonic development of the parathyroids, auditory system and kidneys, and indicate that other GATA family members may be involved in the aetiology of human malformations.

Amino Acid Sequence↗
PubMed2000

Congenital hereditary lymphedema caused by a mutation that inactivates VEGFR3 tyrosine kinase.

Hereditary lymphedema is a chronic swelling of limbs due to dysfunction of lymphatic vessels. An autosomal dominant, congenital form of the disease, also known as "Milroy disease," has been mapped to the telomeric part of chromosome 5q, in the region 5q34-q35. This region contains a good candidate gene for the disease, VEGFR3 (FLT4), that encodes a receptor tyrosine kinase specific for lymphatic vessels. To clarify the role of VEGFR3 in the etiology of the disease, we have analyzed a family with hereditary lymphedema. We show linkage of the disease with markers in 5q34-q35, including a VEGFR3 intragenic polymorphism, and we describe an A-->G transition that cosegregates with the disease, corresponding to a histidine-to-arginine substitution in the catalytic loop of the protein. In addition, we show, by in vitro expression, that this mutation inhibits the autophosphorylation of the receptor. Thus, defective VEGFR3 signaling seems to be the cause of congenital hereditary lymphedema linked to 5q34-q35.

Amino Acid Sequence↗
PubMed2000

Dicentric chromosome 9 due to tandem duplication of the 9p11-q13 region: unusual chromosome 9 variant.

We report on a 31-year-old mentally retarded woman with minor facial anomalies and a heteromorphic chromosome 9 with tandem duplication of the 9p11-q13 pericentromeric region. To the best of our knowledge, this is the first report of tandem duplication of this region. An identical chromosome 9 morphology was found in the healthy and phenotypically normal sister of the proposita. The usefulness of double-color FISH techniques and the presumed mechanism accounting for the origin of the chromosomal anomaly and for the phenotypic discordance observed between the two sisters are discussed.

Adult↗
PubMed2000

Primary, nonsyndromic vesicoureteric reflux and its nephropathy is genetically heterogeneous, with a locus on chromosome 1.

Primary vesicoureteric reflux (VUR) affects 1%-2% of whites, and reflux nephropathy (RN) causes up to 15% of end-stage renal failure in children and adults. There is a 30-50-fold increased incidence of VUR in first-degree relatives of probands, compared with the general population. We report the results of the first genomewide search of VUR and RN; we studied seven European families whose members exhibit apparently dominant inheritance. We initially typed 387 polymorphic markers spaced, on average, at 10 cM throughout the genome; we used the GENEHUNTER program to provide parametric and nonparametric linkage analyses of affected individuals. The most positive locus spanned 20 cM on 1p13 between GATA176C01 and D1S1653 and had a nonparametric LOD score (NPL) of 5.76 (P=.0002) and a parametric LOD score of 3.16. Saturation with markers at 1-cM intervals increased the NPL to 5.94 (P=.00009). Hence, VUR maps to a locus on chromosome 1. There was evidence of genetic heterogeneity at the chromosome 1 locus, and 12 additional loci were identified genomewide, with P<.05. No significant linkage was found to 6p, where a renal and ureteric malformation locus has been reported, or to PAX2, mutations of which cause VUR in renal-coloboma syndrome. Our results support the hypothesis that VUR is a genetic disorder.

Chromosome Mapping↗
PubMed2000

Isolated supravalvular aortic stenosis: functional haploinsufficiency of the elastin gene as a result of nonsense-mediated decay.

We have used single-strand conformation and heteroduplex analyses of genomic amplimers to identify point mutations within the elastin gene (ELN) in patients with non-syndromic supravalvular aortic stenosis (SVAS) from a total of eight unrelated families. Six novel point mutations were identified. We have collected detailed clinical information on mutation carriers and demonstrated significant non-penetrance in some of the families. Together with the new mutations described here, 14 point mutations have been reported in SVAS patients, and 10 of these result in premature stop codons (PTCs). We have analyzed the expression of ELN alleles in skin fibroblasts from one SVAS patient and shown that PTC mutations indeed result in selective elimination of mutant transcripts. Inhibition of the nonsense-mediated decay mechanism by cycloheximide resulted in the stabilization of mutant elastin mRNA. Allelic inactivation by the ELN mutation in this patient led to an overall decrease of the steady state levels of elastin mRNA. Finally, we have demonstrated reduced synthesis and secretion of tropoelastin by skin fibroblasts from the same SVAS patient. We conclude that PTC mutations in ELN result in nonsense-mediated decay of mutant mRNA in this patient. Given the predominance of PTC mutations in SVAS, we suggest that functional haploinsufficiency may be a pathomechanism underlying most cases of non-syndromic SVAS.

Adolescent↗
PubMed2000

Genetic control of intra-uterine growth.

The expression of a few genes in the human genome depends on whether they are located on the maternal or on the paternal chromosome. This phenomenon is called genomic imprinting. Several of these genes have a role in normal embryonic and fetal growth, as indicated by an abnormal development associated with disturbed genomic imprinting. This has lead to the suggestion that the genomic imprinting has evolved as a mechanism to regulate embryonic and fetal growth.

Animals↗
PubMed2000

Deletion of NKX2.1 gene encoding thyroid transcription factor-1 in two siblings with hypothyroidism and respiratory failure.

Thyroid transcription factor-1 encoded by the NKX2.1 gene is a candidate regulator of thyroid and lung morphogenesis and function in humans. We report 2 female siblings with congenital thyroid dysfunction and recurrent acute respiratory distress carrying a heterozygous deletion of chromosome 14q12-13.3, resulting in haploinsufficiency for the NKX2.1 gene. This observation further supports a physiologic role for thyroid transcription factor-1 in early human thyroid and pulmonary function.

Chromosomes, Human, Pair 14↗