Odile Raoul

Trisomie 21 et superoxyde dismutase-1 (IPO-A): Tentative de localisation sur la sous bande 21 q 22.1☆

Abstract The enzymatic activity of SOD-1 in erythrocytes has been studied in several cases of partial monosomies and full and partial trisomies 21. The following results are obtained: 1. The excess of SOD-1 activity in the case of the regular trisomy 21 is confirmed. 2. In monosomy 21 p ter→21 q 21, the enzymatic activity is normal. 3. In trisomy 21 p ter→21 q 21, the enzymatic activity is equally normal. 4. In trisomy 21 q 22, and more precisely in trisomy 21 q 22.1, the activity is increased. Consequently, the SOD-1 gene locus, previously assigned to chromosome 21, is very likely localised in sub-band 21 q 22.1. Finally, the phenotypic analysis indicates that the trisomy of this sub-band is responsible for a great part of the clinical features of trisomy for the whole chromosome 21. The possible role of the SOD-1 excess in the pathogeny of trisomy 21 is discussed.

Paternal deletion of the GNAS imprinted locus (including Gnasxl ) in two girls presenting with severe pre- and post-natal growth retardation and intractable feeding difficulties

Deletions of the long arm of chromosome 20 are rare. Here, we report on two girls with a very small interstitial deletion of the long arm of chromosome 20 presenting with severe pre- and post-natal growth retardation, intractable feeding difficulties, abnormal subcutaneous adipose tissue, similar facial dysmorphism, psychomotor retardation and hypotonia. Standard cytogenetic studies were normal, but high-resolution chromosomes analysis showed the presence of a chromosome (20)(q13.2–q13.3) interstitial deletion. Karyotypes of both parents were normal. Molecular studies using FISH and microsatellite polymorphic markers showed that the deletion was of paternal origin and was approximatively 4.5 Mb in size. A review of other reported patients with similar deletions of the long arm of chromosome 20 shows that the observed phenotype might be explained in the light of the GNAS imprinted locus in particular by the absence of the Gnasxl paternally imprinted gene and the TFA2PC gene in the deleted genetic interval.

New insights into genotype–phenotype correlation for GLI3 mutations

The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig cephalopolysyndactyly syndrome (GCPS) and Pallister–Hall syndrome (PHS). PHS was first described as a lethal condition associating hypothalamic hamartoma, postaxial or central polydactyly, anal atresia and bifid epiglottis. Typical GCPS combines polysyndactyly of hands and feet and craniofacial features. Genotype–phenotype correlations have been found both for the location and the nature of GLI3 mutations, highlighting the bifunctional nature of GLI3 during development. Here we report on the molecular and clinical study of 76 cases from 55 families with either a GLI3 mutation (49 GCPS and 21 PHS), or a large deletion encompassing the GLI3 gene (6 GCPS cases). Most of mutations are novel and consistent with the previously reported genotype–phenotype correlation. Our results also show a correlation between the location of the mutation and abnormal corpus callosum observed in some patients with GCPS. Fetal PHS observations emphasize on the possible lethality of GLI3 mutations and extend the phenotypic spectrum of malformations such as agnathia and reductional limbs defects. GLI3 expression studied by in situ hybridization during human development confirms its early expression in target tissues.

Failure to detect an 8p22-8p23.1 duplication in patients with Kabuki (Niikawa-Kuroki) syndrome

Kabuki syndrome (KS) is a rare MCA/MR syndrome with an estimated frequency of 1/32 000 in Japan. This syndrome is characterized by postnatal growth retardation, distinctive facial features, dermatoglyphic anomalies, skeletal dysplasia, and mental retardation. The molecular basis of KS remains unknown. Recently, Milunsky and Huang reported on six unrelated patients with a clinical diagnosis of KS and an 8p22–8p23.1 duplication using comparative genomic hybridization and BAC-FISH studies. Also, they suggested that a paracentric inversion may contribute to the occurrence of KS. In the present study, 24 patients with a clinical diagnosis of KS based on Niikawa–Kuroki criteria have been collected. They were tested for the presence of an 8p duplication using the same clones as described by Milunsky and Huang. Our results do not confirm the previously described association between KS and an 8p22–8p23.1 duplication.

Sporadic case of unusual facies, cerebral vascular anomalies and developmental delay.

Université Paris Descartes, Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, rue de Sèvres, Paris Cedex, France and Department of Biopathology and Diagnostic Imaging, Tor Vergata University, Rome, Italy Correspondence to Stanislas Lyonnet, MD, Hôpital Necker-Enfants-Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France Tel: + 33 1 444 95136; fax: + 33 1 444 95150; e-mail: stanislas.lyonnet@inserm.fr

Reconnaissance des chromosomes du groupe G par la méthode de dénaturation ménagée

Abstract The new technique, Giemsa staining after heating, has been used for the recognition of the G group chromosomes in man.