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Nisha Limaye,
N Revencu, N Van Regemorter,
M Garzon,
M Bonduelle,
W Chung,
M D Daras,
M C Fahey,
C Garrett,
Y Gillerot, [......],
D Battaglia,
K Heimda,
W Lissens,
E Taub,
L Van Maldergem,
W Van Paesschen,
D Wieczorek,
N W Wood,
L Boon,
M Vikkula
Human Genetics 01/2008; 122(5):549-50. · 5.07 Impact Factor
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ABSTRACT: To compare the diagnostic accuracy of two-dimensional (2D) ultrasound and three-dimensional (3D) computed tomography (CT) for the diagnosis of fetal skeletal anomalies.
Eleven pregnant women underwent 2D ultrasound and 3D-CT. Ten fetuses presented skeletal anomalies on 2D ultrasound and one fetus had a normal ultrasound exam but a familial history of osteopetrosis. We compared retrospectively the diagnoses established on 2D ultrasound and 3D-CT with the neonatal and/or postmortem work-up, which were used as the gold standard.
2D ultrasound provided the correct diagnosis in only two of the 11 cases. CT yielded the correct diagnosis in eight; in six of these, 2D ultrasound had been inconclusive. 3D-CT was more accurate than was 2D ultrasound in visualizing vertebral anomalies (abnormal shape of the vertebral bodies, abnormal interpedicular distance), pelvic bone malformations (delayed ossification of the pubic bones, abnormal acetabular shape) and enlarged metaphysis or synostoses in long bones. In three cases, neither 2D ultrasound nor CT provided the correct diagnosis.
In this series, which included a variety of skeletal dysplasias, 3D-CT had a better diagnostic yield than did 2D ultrasound. Both imaging techniques are useful in the management of fetal dysplasia; 2D ultrasound is a useful screening test and 3D-CT is a valuable complementary diagnostic tool.
Ultrasound in Obstetrics and Gynecology 06/2007; 29(5):537-43. · 3.01 Impact Factor
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ABSTRACT: The aim of this study was to determine whether karyotyping should be performed for every fetal malformation detected in low risk populations.
A karyotype was obtained from 428 fetuses examined over a 10-year period after fetal malformation was diagnosed using obstetrical ultrasound. These fetuses were separated into two groups, one with isolated malformations and the other with multiple malformations. The association between each type of malformation and the result of karyotype was evaluated.
Forty-eight chromosomal abnormalities were encountered in 428 fetuses (11.2%). The karyotype was abnormal in 32/343 (9.3%) fetuses with isolated malformations and 16/85 (18.8%) fetuses with multiple malformations (p=0.022). The probability of an abnormal karyotype among the group of isolated malformation depended on the anatomical system involved (p<0.001). Our study demonstrated several isolated malformations without chromosomal abnormality (hydronephrosis with high obstruction, unilateral multicystic dysplastic kidney, gastroschisis, intestinal dilatation, meconium peritonitis, cystic adenomatoid malformation, pulmonary sequestration, tumor, vertebral anomaly).
Each fetus with multiple malformations needs a chromosomal analysis. Within the group of isolated malformations, our study emphasizes that medical maternal history and the type of malformation need to be taken into account before performing a fetal karyotype.
Prenatal Diagnosis 07/2005; 25(7):567-73. · 2.11 Impact Factor
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ABSTRACT: Familial porencephaly is a rare condition usually transmitted as an autosomal dominant trait with incomplete penetrance. We describe a new family in which six members across four generations had congenital hemiplegia. Cerebral imaging was performed in three patients and showed porencephaly in all cases. In order to provide effective genetic counseling, three asymptomatic carriers were investigated by cerebral computerized tomography (three patients) and cerebral magnetic resonance imaging (one patient). These investigations failed to show any congenital abnormalities. We conclude that cerebral imaging is unreliable to detect obligate carriers of familial porencephaly.
American Journal of Medical Genetics 11/2002; 112(2):198-202.
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ABSTRACT: Created in 1987, the department of medical genetics finds its origins in molecular endocrinology research which had developed from the seventies at the Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (IRIBHM) of the Faculty of Medicine. After its fusion with the Center of Human Genetics of the ULB, in 1992, the department is composed of three units: the lab of molecular genetics and oncology, the lab of cytogenetics and a clinical genetics unit. One thousand consultations of genetic counseling and more than 15,000 molecular or cytogenetic diagnostic procedures are performed annually. The development of the clinical activities was paralleled by a very active research activity, resulting in a series of "firsts". Amongst the main results are: the identification of the first mutations responsible for congenital hypothyroidism; the molecular cloning of the TSH receptor and of a series of "orphan" G protein-coupled receptors; the identification of a novel neuropeptide, nociceptin, by the first example of "reverse pharmacology"; the identification of olfactory receptors on the sperm of mammals, including man; the identification in molecular terms of the mechanisms responsible for acquired and hereditary hyperthyroidisms; the identification of the chemokine receptor CCR5 as the major coreceptor of HIV-1, and of the prevalent mutation of CCR5 conferring resistance to HIV to about 1% of the European population.
Revue medicale de Bruxelles 02/2002; 23 Suppl 2:63-7.
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E De Baere,
M J Dixon,
K W Small,
E W Jabs,
B P Leroy,
K Devriendt,
Y Gillerot,
G Mortier,
F Meire,
L Van Maldergem, [......],
A Verloes,
N Udar,
V Yellore,
M Chalukya,
S Yelchits,
A De Paepe,
F Kuttenn,
M Fellous,
R Veitia,
L Messiaen
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ABSTRACT: Mutations in FOXL2, a forkhead transcription factor gene, have recently been shown to cause blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) types I and II, a rare genetic disorder. In BPES type I a complex eyelid malformation is associated with premature ovarian failure (POF), whereas in BPES type II the eyelid defect occurs as an isolated entity. In this study, we describe the identification of novel mutations in the FOXL2 gene in BPES types I and II families, in sporadic BPES patients, and in BPES families where the type could not be established. In 67% of the patients studied, we identified a mutation in the FOXL2 gene. In total, 21 mutations (17 of which are novel) and one microdeletion were identified. Thirteen of these FOXL2 mutations are unique. In this study, we demonstrate that there is a genotype--phenotype correlation for either types of BPES by the finding that mutations predicted to result in a truncated protein either lacking or containing the forkhead domain lead to BPES type I. In contrast, duplications within or downstream of the forkhead domain, and a frameshift downstream of them, all predicted to result in an extended protein, cause BPES type II. In addition, in 30 unrelated patients with isolated POF no causal mutations were identified in FOXL2. Our study provides further evidence that FOXL2 haploinsufficiency may cause BPES types I and II by the effect of a null allele and a hypomorphic allele, respectively. Furthermore, we propose that in a fraction of the BPES patients the genetic defect does not reside within the coding region of the FOXL2 gene and may be caused by a position effect.
Human Molecular Genetics 08/2001; 10(15):1591-600. · 7.64 Impact Factor
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A F Davies,
G Mirza,
G Sekhon,
P Turnpenny,
F Leroy,
F Speleman,
C Law, N van Regemorter,
E Vamos,
F Flinter,
J Ragoussis
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ABSTRACT: Deletions of the short arm of chromosome 6 are relatively rare, the main features being developmental delay, craniofacial malformations, hypotonia, and defects of the heart and kidney, with hydrocephalus and eye abnormalities occurring in some instances. We present the molecular cytogenetic investigation of six cases with 6p deletions and two cases with unbalanced translocations resulting in monosomy of the distal part of 6p. The breakpoints of the deletions have been determined accurately by using 55 well-mapped probes and fluorescence in situ hybridization (FISH). The cases can be grouped into two distinct categories: interstitial deletions within the 6p22-p24 segment and terminal deletions within the 6p24-pter segment. Characteristics correlating with specific regions are: short neck, clinodactyly or syndactyly, brain, heart and kidney defects with deletions within 6p23-p24; and corneal opacities/iris coloboma/Rieger anomaly, hypertelorism and deafness with deletions of 6p25. The two cases with unbalanced translocations presented with a Larsen-like syndrome including some characteristics of the 6p deletion syndrome, which can be explained by the deletion of 6p25. Such investigation of cytogenetic abnormalities of 6p using FISH techniques and a defined set of probes will allow a direct comparison of reported cases and enable more accurate diagnosis as well as prognosis in patients with 6p deletions.
Human Genetics 02/1999; 104(1):64-72. · 5.07 Impact Factor
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ABSTRACT: Trichothiodystrophy was diagnosed in a 3-year-old male presenting with speech delay, brittle hair, chronic neutropenia, and a history of febrile convulsions. Cranial magnetic resonance imaging revealed a focal subcortical and periventricular gray matter heterotopia. An acute encephalopathy with status epilepticus and coma occurred when he was 4 years of age during an upper respiratory tract infection. Magnetic resonance imaging revealed multifocal T2-weighted hypersignal lesions involving mainly the thalami, hippocampi, midbrain, and pons. Analysis of cerebrospinal fluid revealed hyperproteinorachia without pleocytosis. Results of an extensive metabolic evaluation of this acute brain injury, resembling the syndrome of acute necrotizing encephalopathy of childhood described in Japan, were negative. Focal neuronal migration disorder and acute encephalopathy with symmetric thalamic involvement are newly described neurologic manifestations of syndromes with trichothiodystrophy, which suggests that these conditions may have a common genetic background.
Pediatric Neurology 12/1998; 19(5):392-4. · 1.52 Impact Factor
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ABSTRACT: The 3 affected children from 2 different wedlocks of the mother have been previously described (11). Search by FISH analysis in the mother revealed she is a carrier of balanced translocation of clear terminal G bands of equal sizes of the long arms of chromosomes 10 and 14. Chromosomal slides of the last child (Patient 3) could be analysed by fish and revealed that he did inherit the derivative chromosome 10. He had a partial trisomy 14 and a partial deletion of the long arm of chromosome 10. The clinical pictures correspondence to the possibly abnormal karyotypes will be discussed.
Genetic counseling (Geneva, Switzerland) 02/1998; 9(2):97-102. · 0.50 Impact Factor
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ABSTRACT: Deletions of the short arm of chromosome 6 are relatively rare, only 16 cases having been described in the literature so far. Here we present a detailed investigation by fluorescence in situ hybridisation of two further cases with different but overlapping interstitial deletions involving 6p22, 6p23 and 6p24. The main features involved are craniofacial malformations, heart and kidney defects, mental retardation/developmental delay, hypotonia and hydrocephalus. By using 36 yeast artificial chromosome and cosmid clones from a contig covering 6p22.3-6p25 and other probes with defined cytogenetic locations within 6p21-6p22 we have precisely localised the breakpoints involved in each of the cases, estimated the sizes of the deleted regions and defined the region that is hemizygously deleted in both cases.
Human Genetics 11/1996; 98(4):454-9. · 5.07 Impact Factor
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ABSTRACT: We have characterised a point mutation causing the substitution of serine for glycine at position 661 of the alpha1(I) chain of type I collagen in a child with a severe form of osteogenesis imperfecta. An identical glycine substitution in the alpha2(I) chain was previously detected in a woman with post-menopausal osteoporosis. Two of her sons were heterozygous for the mutation and the third son was homozygous as a result of uniparental isodisomy. Biochemical profiles of the type I collagen heterotrimers were studied in each of the patients and compared with a control. Medium and cell-layer collagens were overmodified in all patients. Overmodification was obvious in the patient with the alpha 1(I) mutation but mild in the patients with the alpha 2(I) mutation, being slightly less evident in the heterozygote than in the homozygote. Investigation of the melting curves of the mutant collagen trimers in all three patients showed the same slight decrease in thermal stability and, hence, a lack of correlation with phenotypic severity. In contrast, the degree of overmodification of the collagen alpha chains was correlated with the phenotypic severity. The clinical observations in these patients illustrate the possibly predominant role of mutations in the collagen alpha1(I) chains over the same mutations in the alpha2(I) chains in determining the clinical outcome.
Human Genetics 04/1996; 97(3):324-9. · 5.07 Impact Factor
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ABSTRACT: Metachromatic leukodystrophy (MLD) is an autosomal recessive disease of myelin metabolism caused by a deficiency in the lysosomal enzyme arylsulphatase A (ARSA). We have identified a new mutation in exon 4 of the ARSA gene of two unrelated Belgian patients with late-infantile MLD. The mutation predicts an aspartic acid-to-histidine substitution at position 255 in arylsulphatase A (D255H), in a highly conserved region among sulphatases. Transient expression of the mutation in COS cells did not show an increase in ARSA activity. Both patients were compound heterozygotes carrying the frequent splice site mutation in intron 2 (459 + IG -->A) on the other allele.
Journal of Inherited Metabolic Disease 01/1996; 19(6):782-6. · 3.58 Impact Factor
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ABSTRACT: We report an association of trigonocephaly and thumb hypoplasia in a 6.5-year-old boy, diagnosed as Baller-Gerold syndrome. In addition to craniosynostosis and radial limb defect, which are constant in this syndrome, our patient presents two unusual features: the first is an epidermal nevus and the second is an agenesis of the middle portion of corpus callosum. This unique type of callosal agenesis in the context of a polymalformative disorder supports the hypothesis that partial agenesis of corpus callosum may be due to an event occurring before the 12th week gestation with continued development of the midline structures.
Neuropediatrics 11/1995; 26(5):273-5. · 0.94 Impact Factor
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ABSTRACT: We have studied a girl with multiple congenital anomalies, growth and mental deficiency, characteristic facial anomalies, cataracts, cerebellar atrophy, and severe hypocholesterolemia. Death occurred at age 7 years. After excluding several syndromes, i.e., peroxisomal disorders, mevalonic acidaemia, and Marinesco-Sjögren syndrome, it is concluded that this girl had severe Smith-Lemli-Opitz Syndrome (SLOS) with exceptionally long survival. This diagnosis was confirmed through assay of 7-dehydrocholesterol in cultured fibroblasts.
American Journal of Medical Genetics 05/1995; 56(3):276-80.
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ABSTRACT: Foetal blood sampling was performed at 35 weeks of gestation due to abnormal foetal ultrasound findings. There was apparent monosomy 21 (45,XX,-21) in all mitoses analyzed. The infant died at 37 weeks during delivery. Examination disclosed facial anomalies, clubfeet, hypoplasia of the left urogenital tract, agenesis of corpus callosum, ventricular dilatation, and heterotopias. Reevaluation of the karyotype showed an unbalanced translocation t(1;21) (q44;q22.11) which resulted from a maternal balanced translocation. These findings were confirmed by fluorescence in situ hybridization and molecular studies with chromosome 21 specific markers. The latter showed a proximal deletion of the maternally derived chromosome 21 including all loci from centromere down to the D21S210 locus. This case illustrates the need for complementary cytogenetic and molecular investigations in cases of apparent monosomy 21.
American Journal of Medical Genetics 08/1994; 51(3):260-5.
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ABSTRACT: The birth of a male baby was induced at 32 weeks. In utero, the child presented, inter alia, signs of hydrops, hepatosplenomegaly and anaemia. Two in utero transfusions for correction of the anaemia were performed at 28 and 29 weeks, respectively. The baby rapidly presented respiratory distress with mixed acidosis. Three hours after birth, pink urine was excreted. Signs of icterus necessitated phototherapy, after which photosensitivity occurred. Erythrocytes were fluorescent under long-wavelength UV light. The baby died 24 hours after birth, displaying severe acidosis, a diffuse haemorrhagic syndrome, and repeated brady-cardia which did not respond to isoprenaline. The analysis of porphyrins in urine, blood and faeces of the baby gave the following results: 1) uroporphyrin (I and III isomeric series) was increased in urine and faeces, with traces in erythrocytes and plasma; 2) heptacarboxyporphyrin I was found mainly in urine and much less in erythrocytes, plasma and faeces; 3) coproporphyrin I was increased in urine, erythrocytes, plasma and faeces, and 4) 5-aminolaevulinic acid and porphobilinogen in urine and plasma were within the reference ranges. Determination of the enzymes of haem biosynthesis in erythrocytes and lymphocytes showed that both parents possessed only 50% of the normal activity of cosynthase. A previously described point mutation in codon 73 was observed in one parent. Fatal cases of neonatal Günther's disease are extremely rare and such an observation, according to our knowledge, is probably one of the first described.
European journal of clinical chemistry and clinical biochemistry: journal of the Forum of European Clinical Chemistry Societies 04/1993; 31(3):121-8.
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ABSTRACT: In this report, we describe three sibs presenting an identical malformation syndrome i.e.: acrocephaly, brachydactyly, prominent metopic ridge, broad depressed nasal bridge, narrow maxillae, obesity and normal intelligence. We discuss the relationship between this combination of clinical signs and symptoms most compatible with the diagnosis of Summitt syndrome and the Carpenter syndrome.
Genetic counseling (Geneva, Switzerland) 02/1992; 3(2):101-5. · 0.50 Impact Factor
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Genetic counseling (Geneva, Switzerland) 02/1992; 3(2):121-5. · 0.50 Impact Factor
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ABSTRACT: Cordocentesis was performed in 234 pregnancies (241 fetuses) for rapid karyotyping. The indication was in 86% of cases: abnormal ultrasound. The abnormality encountered were IUGR (85 fetuses) or morphologic abnormality of the pregnancy (130 fetuses). The other indications were maternal mosaicism, mosaicism in cultured amniotic cells, maternal age (late booking), fragile X syndrome, confirmation of abnormal karyotype obtained by amniocentesis. The fetal karyotype was established in 97.5% (6 failures), 18 karyotypes were abnormal in the group "abnormal ultrasound" (208 pregnancies, 8.6%; 215 fetuses, 8.3%). No maternal complication were observed, there were 6 fetal losses (2.5%).
Journal de Gynécologie Obstétrique et Biologie de la Reproduction 02/1992; 21(2):241-5. · 0.42 Impact Factor
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ABSTRACT: The authors describe a girl with retarded growth, renal malformations, retinal coloboma and hypoplasia of the thumbs like reported in the acro-renal-ocular syndrome. In addition, they found defects of the ribs and spine and cleft palate, not previously described in this syndrome. The was noted to have minor anomalies of the hands, which might represent a mild manifestation of this autosomal dominant syndrome.
Ophthalmic paediatrics and genetics 01/1992; 12(4):183-6.
