Sorbonne Université, INSERM, UMR_S 938 Centre de Recherche Saint Antoine, Assistance Publique - Hôpitaux de Paris (APHP), Hôpital Armand Trousseau, Explorations Fonctionnelles Endocriniennes, Paris, France.
APHP, Hôpital Armand Trousseau, Département de Génétique, UF de Génétique Chromosomique, Paris, France.
J Clin Endocrinol Metab. 2018 Jul 1;103(7):2436-2446. doi: 10.1210/jc.2017-02152.
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.
To describe the clinical overlap between SRS and TS and extensively study the molecular aspects of TS.
We retrospectively collected data on 28 patients with disruption of the 14q32.2 imprinted region, identified in our center, and performed extensive molecular analysis.
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.
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.
银-罗素综合征（SRS）（主要继发于 11p15 分子紊乱）和坦普尔综合征（TS）（继发于 14q32.2 分子紊乱）是印迹疾病，具有表型（产前和产后生长迟缓、早期喂养困难）和分子重叠。
描述 SRS 和 TS 之间的临床重叠，并广泛研究 TS 的分子方面。
我们回顾性收集了我们中心鉴定的 14q32.2 印迹区中断的 28 例患者的数据，并进行了广泛的分子分析。
17 例（60.7%）患者表现为母系单亲二体 14 号染色体和 3 例（10.7%）患者 14q32.2 缺失的错义甲基化。8 例（28.6%）患者存在 MEG3/DLK1 基因间差异甲基化区去甲基化的母源性单亲二体。大多数患者（72.7%）的 Netchine-Harbison SRS 临床评分系统≥4/6，符合 SRS 的临床诊断。女孩的青春期开始年龄平均为 7.2 岁，男孩为 9.6 岁；37.5%有早熟性性早熟。所有患者的体重指数在性早熟前和/或青春期开始时均增加。多基因座分析确定了 58.8%的患者存在多个甲基化缺陷。我们在参与建立或维持 DNA 甲基化的蛋白编码基因中发现了四个潜在的致病性遗传变异。
大多数 14q32.2 缺失的患者符合 SRS 的临床诊断标准。这些临床数据表明，TS 和 SRS 患者的治疗相似，特别注意他们青春期开始时的年龄较小和体重指数的早期增加。
