Chromosome 14q32.2 imprinted region disruption as an alternative molecular diagnosis of Silver-Russell Syndrome.

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Chromosome 14q32.2 imprinted region disruption as an alternative molecular diagnosis of Silver-Russell Syndrome.

J Clin Endocrinol Metab. 2018 Apr 11;:

Authors: Geoffron S, Abi Habib W, Chantot-Bastaraud S, Dubern B, Steunou V, Azzi S, Afenjar A, Busa T, Canton AP, Chalouhi C, Dufourg MN, Esteva B, Fradin M, Geneviève D, Heide S, Isidor B, Linglart A, Morice Picard F, Naud-Saudreau C, Oliver Petit I, Philip N, Pienkowski C, Rio M, Rossignol S, Tauber M, Thevenon J, Vu-Hong TA, Harbison MD, Salem J, Brioude F, Netchine I, Giabicani E

Abstract
Context: Silver-Russell syndrome (SRS) (mainly secondary to 11p15 molecular disruption) and Temple syndrome (TS) (secondary to 14q32.2 molecular disruption) are imprinting disorders with phenotypic (prenatal and postnatal growth retardation, early feeding difficulties) and molecular overlap.
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 and 37.5% had premature pubarche. The body mass index (BMI) 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 TS and SRS patients with special attention to their young age at the onset of puberty and early increase of BMI.

PMID: 29659920 [PubMed - as supplied by publisher]

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