Social, neurodevelopmental, endocrine, and head size differences associated with atypical deletions in Williams-Beuren syndrome.
Social, neurodevelopmental, endocrine, and head size differences associated with atypical deletions in Williams-Beuren syndrome.
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DOI：
10.1002/ajmg.a.61522
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发表时间：
2020-05
期刊：
影响因子：
--
通讯作者：
Kozel BA
中科院分区：
文献类型：
--
作者：
Lugo M;Wong ZC;Billington CJ Jr;Parrish PCR;Muldoon G;Liu D;Pober BR;Kozel BA
Williams-Beuren综合征（WBS）是由7q11.23上的26-28个基因的半合子缺失引起的多系统疾病。估计2-5%的患者具有“非典型”缺失，其从WBS关键区域向着丝粒和/或端粒方向延伸。为了阐明这些缺失类型之间的临床差异，我们评估了我们队列中的10例非典型缺失患者和17例文献中描述的类似分类缺失患者。在任一方向上较大的缺失通常导致更严重的发育迟缓，而包含MAGI 2的缺失与患者的婴儿痉挛和癫痫发作有关。此外，在着丝粒缺失（包括AUTS 2）的小鼠中，头部尺寸明显较小。由于非典型缺失的儿童被注意到社会参与较少，我们还试图确定非典型缺失与社会表型的关系。使用社会反应量表-2，评分员将非典型缺失的个体评分为具有与典型WBS缺失的个体不同的社会特征（p = 0.001），非典型缺失组的社会动机得分更高（更多受损）（p = 0.005）。通过识别这些区别，医生可以更好地识别患者，包括那些可能已经进行临床或FISH WBS诊断的患者，这些患者可能会从额外的分子评估，筛查和治疗中受益。除了临床表现外，我们还注意到轻度内分泌表现不同于在几个端粒缺失（包括POR）患者的WBS中常见的表现。需要对其他端粒缺失病例进行进一步研究以证实这一观察结果。
Williams–Beuren syndrome (WBS) is a multisystem disorder caused by a hemizygous deletion on 7q11.23 encompassing 26–28 genes. An estimated 2–5% of patients have “atypical” deletions, which extend in the centromeric and/or telomeric direction from the WBS critical region. To elucidate clinical differentiators among these deletion types, we evaluated 10 individuals with atypical deletions in our cohort and 17 individuals with similarly classified deletions previously described in the literature. Larger deletions in either direction often led to more severe developmental delays, while deletions containing MAGI2 were associated with infantile spasms and seizures in patients. In addition, head size was notably smaller in those with centromeric deletions including AUTS2. Because children with atypical deletions were noted to be less socially engaged, we additionally sought to determine how atypical deletions relate to social phenotypes. Using the Social Responsiveness Scale-2, raters scored individuals with atypical deletions as having different social characteristics to those with typical WBS deletions (p = .001), with higher (more impaired) scores for social motivation (p = .005) in the atypical deletion group. In recognizing these distinctions, physicians can better identify patients, including those who may already carry a clinical or FISH WBS diagnosis, who may benefit from additional molecular evaluation, screening, and therapy. In addition to the clinical findings, we note mild endocrine findings distinct from those typically seen in WBS in several patients with telomeric deletions that included POR. Further study in additional telomeric deletion cases will be needed to confirm this observation.
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影响因子：
12.3
作者：
Kuilman T;Velds A;Kemper K;Ranzani M;Bombardelli L;Hoogstraat M;Nevedomskaya E;Xu G;de Ruiter J;Lolkema MP;Ylstra B;Jonkers J;Rottenberg S;Wessels LF;Adams DJ;Peeper DS;Krijgsman O
通讯作者：
Krijgsman O
DOI：
10.1002/ajmg.a.40494
发表时间：
2018-10
期刊：
American journal of medical genetics. Part A
影响因子：
--
作者：
Cohen JL;Crowley TB;McGinn DE;McDougall C;Unolt M;Lambert MP;Emanuel BS;Zackai EH;McDonald-McGinn DM
通讯作者：
McDonald-McGinn DM
影响因子：
30.8
作者：
Coe, Bradley P.;Stessman, Holly A. F.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
影响因子：
1.5
作者：
Komoike, Yuta;Fujii, Katsunori;Yamamoto, Toshiyuki
通讯作者：
Yamamoto, Toshiyuki
影响因子：
25
作者：
Barak, Boaz;Zhang, Zicong;Feng, Guoping
通讯作者：
Feng, Guoping