Showing papers by "Alain Verloes published in 1998"

Paternal Uniparental Disomy for Chromosome 1 Revealed by Molecular Analysis of a Patient with Pycnodysostosis

Abstract: Molecular analysis of a patient affected by the autosomal recessive skeletal dysplasia, pycnodysostosis (cathepsin K deficiency; MIM 265800), revealed homozygosity for a novel missense mutation (A277V). Since the A277V mutation was carried by the patient's father but not by his mother, who had two normal cathepsin K alleles, paternal uniparental disomy was suspected. Karyotyping of the patient and of both parents was normal, and high-resolution cytogenetic analyses of chromosome 1, to which cathepsin K is mapped, revealed no abnormalities. Evaluation of polymorphic DNA markers spanning chromosome 1 demonstrated that the patient had inherited two paternal chromosome 1 homologues, whereas alleles for markers from other chromosomes were inherited in a Mendelian fashion. The patient was homoallelic for informative markers mapping near the chromosome 1 centromere, but he was heteroallelic for markers near both telomeres, establishing that the paternal uniparental disomy with partial isodisomy was caused by a meiosis II nondisjunction event. Phenotypically, the patient had normal birth height and weight, had normal psychomotor development at age 7 years, and had only the usual features of pycnodysostosis. This patient represents the first case of paternal uniparental disomy of chromosome 1 and provides conclusive evidence that paternally derived genes on human chromosome 1 are not imprinted.

Central nervous system malformations and early end‐stage renal disease in oro‐facio‐digital syndrome type I: A review

Abstract: Intracerebral cysts and porencephaly or arachnoid cysts are rarely but are repeatedly reported in orofaciodigital (OFD) syndrome type 1. We report on 2 families in which OFD syndrome type 1 was observed with central nervous system (CNS) malformations and 3 sporadic cases of OFD with CNS defects, most likely representing fresh mutations for OFD 1. In one case, vermis hypoplasia was present; in another, periventricular heterotopiae were noted. We review the literature on CNS anomalies in OFD syndromes and stress the difficulties in genetic counseling and functional prognosis for children of OFD 1 female carriers prenatally diagnosed with a malformation of the brain. As for CNS malformations, renal cystic disease is an often overlooked complication specific to OFD 1. In 1 family, cystic medullary disease was noted in OFD 1 carriers, leading 1 patient to dialysis by age 35 years and the other to severe renal insufficiency by age 28 years. Longitudinal follow-up of OFD 1 carriers should be performed, and renal function should be assessed in those with cysts because the functional prognosis of this developmental anomaly may be worse than usually reported in the literature.

Pfeiffer syndrome type 2 : Further delineation and review of the literature

Abstract: We present 5 unrelated patients, 3 boys and 2 girls, with Pfeiffer syndrome (PS) type 2. They all had cloverleaf skull, severe proptosis, ankylosis of the elbows, broad thumbs and/or broad halluces and variable accompanying anomalies. We review the literature on all subtypes of PS. Most patients with PS type 2 died shortly after birth. Causes of death include pulmonary problems, brain abnormalities, prematurity and post-operative complications. DNA studies were performed in 3 of the 5 patients. Two of them showed a 1036T --> C mutation in the fibroblast growth factor receptor 2 (FGFR2) gene, that was earlier reported in PS and in Crouzon syndrome. Probably most, if not all, PS type 2 cases are caused by a de novo mutation in the FGFR2 gene or in another, yet unidentified gene. To date all type 2 cases have been non-familial. A low recurrence risk for parents can be advised.

Juvenile rheumatoid arthritis and del(22q11) syndrome: a non-random association.

Abstract: Del(22q11) is a common microdeletion syndrome with an extremely variable phenotype. Besides classical manifestations, such as velocardiofacial (Shprintzen) or DiGeorge syndromes, del(22q11) syndrome may be associated with unusual but probably causally related anomalies that expand its phenotype and complicate its recognition. We report here three children with the deletion and a chronic, erosive polyarthritis resembling idiopathic cases of juvenile rheumatoid arthritis (JRA). Patient 1, born in 1983, initially presented with developmental delay, facial dysmorphism, velopharyngeal insufficiency, and severe gastro-oesophageal reflux requiring G tube feeding. From the age of 3 years, he developed JRA, which resulted in severe restrictive joint disease, osteopenia, and platyspondyly. Patient 2, born in 1976, had tetralogy of Fallot and peripheral pulmonary artery stenosis. She developed slowly, had mild dysmorphic facial features, an abnormal voice, and borderline intelligence. JRA was diagnosed at the age of 5 years. The disorder followed a subacute course, with relatively mild inflammatory phenomena, but an extremely severe skeletal involvement with major osteopenia, restrictive joint disease (bilateral hip replacement), and almost complete osteolysis of the carpal and tarsal bones with phalangeal synostoses, leading to major motor impairment and confinement to a wheelchair. Patient 3, born in 1990, has VSD, right embryo-toxon, bifid uvula, and facial dysmorphism. She developed JRA at the age of 1 year. She is not mentally retarded but has major speech delay secondary to congenital deafness inherited from her mother. In the three patients, a del(22q11) was shown by FISH analysis. These observations, and five other recently published cases, indicate that a JRA-like syndrome is a component of the del(22q11) spectrum. The deletion may be overlooked in those children with severe, chronic inflammatory disorder.

Bruck syndrome: neonatal presentation and natural course in three patients.

Abstract: Three unrelated patients with congenital arthrogryposis and brittle bones, the main neonatal signs of Bruck syndrome, are presented. In infancy and early childhood recurrent fractures of ribs and long bones and persistent Wormian bones in the calvarium are reminiscent of osteogenesis imperfecta (OI) even with white sclerae, normal dental quality and normal hearing as important clinical negatives. The diagnosis was made before two years of age in two, and in adolescence in the third patient. The latter's radiologically documented long-term natural course reveals slow progressivity of osteopenia and growth deficiency, worsening tendon contractures and pterygia in addition to increasing spine and pelvis deformation. Mental development remains normal. Bruck syndrome is monogenic and probably due to homozygosity of an as yet unidentified gene. As no alteration in the collagens I and III is detected and molecular screening reveals no mutation in the COL1A1 and COL1A2 genes, the pathogenesis of this severe disorder of connective tissue remains largely unknown.

Prenatal diagnosis of pyruvate carboxylase deficiency by direct measurement of catalytic activity on chorionic villi samples

Abstract: Pyruvate carboxylase (PC) deficiency is a rare metabolic disorder in infants and children, most frequently with fatal outcome. Its prenatal diagnosis by radiometric assay in cultured amniocytes has previously been reported. We present and discuss the prenatal diagnosis of PC deficiency by direct measurement of PC activity in chorionic villi, in two subsequent pregnancies in a family who previously lost a child affected by PC deficiency. In the next pregnancy PC was unmeasurably low in chorionic villi whereas in control samples its activity was between 0.8 and 3.3 nmol min-1 mg protein-1. Following elective termination of the pregnancy PC was shown to be totally inactive in post-mortem fetal liver. In the most recent pregnancy of the proband's mother PC was normally active in the chorionic villi. The product of this pregnancy was a normal boy.

[Programs of systematic screening in neonatology. Pharmaco-economic aspects].

Abstract: Systematic neonatal screening offers many advantages for the patients, its family and the community. The Genetic center of the University Hospital of Liege provides neonatal screening for the following diseases: phenylketonuria, congenital hypothyroidy, cystic fibrosis, alpha-1-antitrypsin, adrenal hyperplasia and biotinidase deficiency. On economical grounds, it is clear that the organisation of neonatal screening costs less to the community than the cost of the disease if diagnosis is made too late as to allow an alleviation, or even a total recovery, of the symptomatology.

Le cas clinique du mois Un homme a caryotype 46,XX.

Abstract: The XX males represent a rare expression of the Klinefelter syndrome associated with hypergonadotropic hypogonadism. Generally the patients are of small stature with normal secondary sexual male features but with small testes and constant sterility. The plasma concentrations of FSH and LH are very high in accordance with the decrease of the testicular function. From the genetic point of view, the XX males may be divided in 3 groups: 1) in 80% of cases, the XX males bear the SRY gene and exhibit a XY translation during the paternal meiosis with the presence of the SRY gene on one of the X chromosomes as a marker of the male differentiation; 2) in 10% of cases, the males are (SRY-)XX; the abnormal development is then due to other genes than the TDF, which, when mutated, can induce sexual male differentiation. The remaining 10% of cases are due to chromosomal mosaicism with more XX than XY.