Williams–Beurens syndrome (WBS) is a rare genetic disorder caused by a recurrent 7q11.23 microdeletion. Clinical characteristics include typical facial dysmorphisms, weakness of connective tissue, short stature, mild to moderate intellectual disability and distinct behavioral phenotype. Cardiovascular diseases are common due to haploinsufficiency of ELN gene. A few cases of larger or smaller deletions have been reported spanning towards the centromeric or the telomeric regions, most of which included ELN gene. We report on three patients from two unrelated families, presenting with distinctive WBS features, harboring an atypical distal deletion excluding ELN gene. Our study supports a critical role of CLIP2, GTF2IRD1, and GTF2I gene in the WBS neurobehavioral profile and in craniofacial features, highlights a possible role of HIP1 in the autism spectrum disorder, and delineates a subgroup of WBS individuals with an atypical distal deletion not associated to an increased risk of cardiovascular defects.

中文翻译：

---

不包括ELN基因的非典型7q11.23缺失导致Williams–Beuren综合征颅面特征和神经认知特征

威廉姆斯—布伦斯综合症（WBS）是一种罕见的遗传病，由反复发生的7q11.23微缺失引起。临床特征包括典型的面部畸形，结缔组织无力，身材矮小，轻度至中度智力障碍和独特的行为表型。由于ELN基因的单倍不足，心血管疾病是常见的。据报道，有几个较大或较小缺失的案例，涉及着丝粒或端粒区域，其中大多数包括ELN基因。我们报告了来自两个无关家庭的三名患者，这些患者具有独特的WBS功能，具有不典型的远端缺失，不包括ELN基因。我们的研究支持的关键作用CLIP2，GTF2IRD1，以及WTF神经行为特征和颅面特征中的GTF2I基因，突出显示了HIP1在自闭症谱系障碍中的可能作用，并描绘了具有非典型性远端缺失的WBS个体亚群，与心血管缺陷风险增加无关。