Department of Clinical Genetics, Shengjing Hospital of China Medical University, No 36 Sanhao Street, Heping Ward, Shenyang, 110004, China.
Department of Developmental Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.
Ital J Pediatr. 2022 Jul 23;48(1):121. doi: 10.1186/s13052-022-01319-1.
Prader-Willi syndrome (PWS) is a complex disorder caused by impaired paternally expressed genes on chromosome 15q11-q13. Variable findings have been reported about the phenotypic differences among PWS genetic subtypes.
A total of 110 PWS patients were diagnosed from 8,572 pediatric patients included from July 2013 to December 2021 by MLPA and MS-MLPA assays. Atypical deletions were defined by genomic CNV-sequencing. Maternal uniparental disomy (UPD) was subgrouped by microsatellite genotyping. Clinical data were collected for phenotype-genotype associations. Twenty-one patients received growth hormone (GH) treatment, and the anthropometric and laboratory parameters were evaluated and compared.
Genetically, the 110 patients with PWS included 29 type I deletion, 56 type II deletion, 6 atypical deletion, 11 heterodisomy UPD, and 8 isodisomy UPD. The UPD group had significantly higher maternal age (31.4 ± 3.4 vs 27.8 ± 3.8 years), more anxiety (64.29% vs 26.09%) and autistic traits (57.14% vs 26.09%), and less hypopigmentation (42.11% vs 68.24%) and skin picking (42.86% vs 71.01%) than the deletion group. The type I deletion group was diagnosed at earlier age (3.7 ± 3.3 vs 6.2 ± 3.2 years) and more common in speech delay (95.45% vs 63.83%) than the type II. The isodisomy UPD group showed a higher tendency of anxiety (83.33% vs 50%) than the heterodisomy. GH treatment for 1 year significantly improved the SDS of height (- 0.43 ± 0.68 vs - 1.32 ± 1.19) and IGF-I (- 0.45 ± 0.48 vs - 1.97 ± 1.12). No significant changes were found in thyroid function or glucose/lipid metabolism.
We explored the physical, psychological and behavioral phenotype-genotype associations as well as the GH treatment effect on PWS from a large cohort of Chinese pediatric patients. Our data might promote pediatricians' recognition and early diagnosis of PWS.
普拉德-威利综合征（PWS）是一种由 15q11-q13 染色体上父源表达基因缺陷引起的复杂疾病。已有报道称，不同 PWS 遗传亚型之间存在表型差异。
通过多重连接探针扩增（MLPA）和 MS-MLPA 检测，从 2013 年 7 月至 2021 年 12 月纳入的 8572 例儿科患者中，共诊断出 110 例 PWS 患者。通过基因组 CNV-测序定义非典型缺失。微卫星基因分型亚组化母源单亲二体（UPD）。收集临床资料进行表型-基因型关联分析。21 例患者接受生长激素（GH）治疗，评估并比较其人体测量学和实验室参数。
在基因层面，110 例 PWS 患者中包括 29 例 I 型缺失、56 例 II 型缺失、6 例非典型缺失、11 例单亲二体 UPD 和 8 例同源二体 UPD。UPD 组的母亲年龄明显更高（31.4±3.4 岁 vs 27.8±3.8 岁）、焦虑症（64.29% vs 26.09%）和自闭症特征（57.14% vs 26.09%）更多，而色素减退（42.11% vs 68.24%）和皮肤搔抓（42.86% vs 71.01%）更少。I 型缺失组的诊断年龄更早（3.7±3.3 岁 vs 6.2±3.2 岁），且语言发育迟缓更为常见（95.45% vs 63.83%）。同型二体 UPD 组比异源二体 UPD 组更易出现焦虑（83.33% vs 50%）。GH 治疗 1 年，身高 SDS（-0.43±0.68 岁 vs-1.32±1.19 岁）和 IGF-I（-0.45±0.48 岁 vs-1.97±1.12 岁）显著改善。甲状腺功能或葡萄糖/脂质代谢未发现明显变化。
本研究从中国儿科患者的大样本中探讨了 PWS 的体格、心理和行为表型-基因型关联以及 GH 治疗效果。我们的数据可能有助于儿科医生对 PWS 的认识和早期诊断。
