Prader-Willi syndrome and atypical submicroscopic 15q11-q13 deletions with or without imprinting defects
Prader-Willi syndrome and atypical submicroscopic 15q11-q13 deletions with or without imprinting defects
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DOI：
10.1016/j.ejmg.2016.09.017
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发表时间：
2016-11-01
影响因子：
1.9
通讯作者：
Butler, Merlin G.
中科院分区：
文献类型：
--
作者：
Hassan, Maaz;Butler, Merlin G.
我们报告了对一名现年 26 岁的白人女性进行的 20 年随访，该女性患有 Prader-Willi 综合征 (PWS)，该女性在 1996 年首次检测到大小为 100-200 kb 的非典型 15q11-q13 亚显微缺失，涉及印记中心、SNRPN 基因和周围区域。 PWS 是一种罕见的复杂疾病，由 15q11-q13 区域父系表达基因缺失引起。通过高分辨率染色体微阵列和甲基化特异性 MLPA 分析，我们更新了患者的基因发现，发现了 209,819bp 的缺失，其中包括 SNURF-SNRPN 基因复合体，其中包括印记中心和 SNORD116 区域。我们与文献中其他四位类似报道的个体进行了比较，这些个体在该区域内具有非典型亚显微缺失，但没有印记中心参与，以更好地表征导致 PWS 临床结果的特定遗传病变。临床上，该患者符合 PWS 的诊断标准，包括婴儿肌张力低下、吸吮不良且喂养困难、整体发育迟缓和觅食较晚、儿童肥胖、手小和抓皮肤。在所有五个病例中，在 15q11-q13 区域都发现了大小相当的小非典型缺失，尽管我们的患者存在印记缺陷，但仍发现了类似的行为/身体特征。这些结果进一步支持了一个重叠的关键删除区域，该区域涉及非编码 snoRNA SNORD116，该区域在五个个体中共有，在 PWS 表型的形成中发挥着关键作用。 (C) 2016 Elsevier Masson SAS。版权所有。
We report a 20 year follow up on a Caucasian female, now 26 years of age, with Prader-Willi syndrome (PWS) harboring an atypical 15q11-q13 submicroscopic deletion of 100e200 kb in size first detected in 1996 involving the imprinting center, SNRPN gene and surrounding region. PWS is a rare complex disorder caused by the loss of paternally expressed genes in the 15q11-q13 region. With high resolution chromosomal microarray and methylation - specific MLPA analysis, we updated the genetic findings on our patient and found a 209,819bp deletion including the SNURF-SNRPN gene complex which includes the imprinting center and the SNORD116 region. We compared with four other similarly reported individuals in the literature with atypical submicroscopic deletions within this region but without imprinting center involvement to better characterize the specific genetic lesions causing PWS clinical findings. Clinically, our patient met the diagnostic criteria of PWS including infantile hypotonia, a poor suck with feeding difficulties, global developmental delays and later food foraging, childhood obesity, small hands and skin picking. Small atypical deletions of comparable sizes were seen in the 15q11-q13 region in all five cases and similar behavioral/physical characteristics were found despite an imprinting defect in our patient. These results further support an overlapping critical deletion region involving the non-coding snoRNA SNORD116 in common in the five individuals playing a key role in contributing to the PWS phenotype. (C) 2016 Elsevier Masson SAS. All rights reserved.