期刊
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
卷 182, 期 5, 页码 1008-1020出版社
WILEY
DOI: 10.1002/ajmg.a.61522
关键词
atypical deletion; autism spectrum; microcephaly; phenotype; social behavior; Williams-Beuren syndrome
资金
- Children's Discovery Institute [CDI-LI-2016-569, CH-FR2011-169, MD-II-2013-269]
- Heartland Genetics Services Collaborative [H46MC24089]
- National Institutes of Health [U01 HG010215, ZIA-HL006212]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZIAHL006212] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [ZIEHG200354] Funding Source: NIH RePORTER
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据