title: A new 17p13.3 microduplication including the PAFAH1B1 and YWHAE genes resulting from an unbalanced X;17 translocation.
abstract: Submicroscopic duplications of the genomic interval deleted in Miller-Dieker syndrome (MDS) were recently identified by array-based comparative genomic hybridization (a-CGH) studies, describing new genomic disorders in the MDS locus. These rearrangements of varying size, from 59-88 kb to 4 Mb, were non-recurrent, and appear to result from diverse molecular mechanisms. Only five patients had overlapping 17p13.3 duplications including the entire MDS critical region. We describe here a 13-year-old girl with a novel microduplication of the MDS critical region, involving the PAFAH1B1 and YWHAE genes. She presented with moderate psychomotor retardation, speech delay, behavioral problems, and bilateral cleft lip and palate, a previously unreported manifestation. Initially diagnosed as having an apparently simple terminal Xq26 deletion on standard cytogenetic analysis, she was found to have an associated terminal 4.2 Mb 17p13.3 submicroscopic duplication, identified by subtelomere FISH analysis, further characterized by high-resolution array CGH, resulting from an unbalanced X;17 translocation. Phenotypic comparison with the 5 other patients previously described, revealed common phenotypic features, such as hypotonia, mild to moderate developmental delay/mental retardation, speech abnormalities, behavioral problems, recurrent infections, relatively increase of body weight, discrete facial dysmorphism including downslanting palpebral fissures, broad midface, pointed chin, contributing to further delineate this new 17p13.3 microduplication syndrome.
authors.affiliation: Service de Génétique et Embryologie médicales, Hôpital Armand Trousseau, APHP, UPMC, Paris, France.
authors.forename: Capucine
authors.initials: C
authors.lastname: Hyon
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marlin
authors.forename: Sandra
authors.initials: S
authors.lastname: Chantot-Bastaraud
authors.forename: Philippe
authors.initials: P
authors.lastname: Mabboux
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Beaujard
authors.forename: Essam
authors.initials: E
authors.lastname: Al Ageeli
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Vazquez
authors.forename: Arnaud
authors.initials: A
authors.lastname: Picard
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Siffroi
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Portnoï
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D048948:14-3-3 Proteins / Q000235:genetics*; D000293:Adolescent; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D041321:Chromosomes, Human, X / Q000235:genetics; D054221:Classical Lissencephalies and Subcortical Band Heterotopias / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D005260:Female; D020440:Gene Duplication; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D013577:Syndrome; D014178:Translocation, Genetic
chemical_list: D048948:14-3-3 Proteins; D008869:Microtubule-Associated Proteins; C482983:YWHAE protein, human; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human