Chromosome 14q32.2 Imprinted Region Disruption as an Alternative Molecular Diagnosis of Silver-Russell Syndrome.
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Geoffron Sophie, Abi Habib Walid, Chantot-Bastaraud Sandra, Dubern Béatrice, Steunou Virginie, Azzi Salah, Afenjar Alexandra, Busa Tiffanny, Pinheiro Canton Ana, Chalouhi Christel, Dufourg Marie-Noëlle, Esteva Blandine, Fradin Mélanie, Geneviève David, Heide Solveig, Isidor Bertrand, Linglart Agnès, Morice Picard Fanny, Naud-Saudreau Catherine, Oliver Petit Isabelle, Philip Nicole, Pienkowski Catherine, Rio Marlène, Rossignol Sylvie, Tauber Maithé, Thevenon Julien, Vu-Hong Thuy-Ai, Harbison Madeleine D, Salem Jennifer, Brioude Frédéric, Netchine Irène, Giabicani Eloïse
Аннотация
OBJECTIVE: To describe the clinical overlap between SRS and TS and extensively study the molecular aspects of TS.
PATIENTS: We retrospectively collected data on 28 patients with disruption of the 14q32.2 imprinted region, identified in our center, and performed extensive molecular analysis.
RESULTS: Seventeen (60.7%) patients showed loss of methylation of the MEG3/DLK1 intergenic differentially methylated region by epimutation. Eight (28.6%) patients had maternal uniparental disomy of chromosome 14 and three (10.7%) had a paternal deletion in 14q32.2. Most patients (72.7%) had a Netchine-Harbison SRS clinical scoring system ≥4/6, and consistent with a clinical diagnosis of SRS. The mean age at puberty onset was 7.2 years in girls and 9.6 years in boys; 37.5% had premature pubarche. The body mass index of all patients increased before pubarche and/or the onset of puberty. Multilocus analysis identified multiple methylation defects in 58.8% of patients. We identified four potentially damaging genetic variants in genes encoding proteins involved in the establishment or maintenance of DNA methylation.
CONCLUSIONS: Most patients with 14q32.2 disruption fulfill the criteria for a clinical diagnosis of SRS. These clinical data suggest similar management of patients with TS and SRS, with special attention to their young age at the onset of puberty and early increase of body mass index.