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Abstract：
Recently, an autosomal recessive subtype of connective tissue disorder within the spectrum of Ehlers-Danlos syndrome (EDS), named classical-like EDS type 2 (clEDS2), was identified. clEDS2 is associated with biallelic variants in the adipocyte enhancer binding protein 1 (AEBP1) gene, specifically, affecting its aortic carboxypeptidase-like protein (ACLP) isoform. We described the 15th patient (13th family) diagnosed with clEDS2. This patient presented with notable similarities in phenotype to the documented cases, along with additional characteristics such as significant prematurity and short stature. An EDS sequencing panel-based analysis revealed homozygous AEBP1: NM_001129.5:c.2923del, p.Ala975Profs*22 likely pathogenic variants, and maternally inherited heterozygous COL11A1: NM_001854.4:c.1160A>G, p.Lys387Arg variant of uncertain significance in our patient. Upon comprehensive review of all previously reported clEDS2 patients, our patient exhibited the following overlapping phenotypes, including cutaneous features: hyperextensibility, atrophic scars/delayed wound healing (100%), easy bruising (100%), excessive skin (93%); skeletal features: generalized joint hypermobility (93%), pes planus (93%), dislocation/subluxation (93%); and cardiovascular features (86%). Our patient did not display symptoms of the critical complications reported in a few individuals, including superior mesenteric artery aneurysms and ruptures, aortic root aneurysm/dissection, spontaneous pneumothoraxes, and bowel ruptures. Together, this case expands the genetic and clinical phenotypic spectrum of AEBP1-related clEDS2.
摘要：
最近,Ehlers-Danlos综合征（EDS）范围内的结缔组织疾病的常染色体隐性亚型，命名为类似经典的EDS类型2（clEDS2），已确定。clEDS2与脂肪细胞增强子结合蛋白1（AEBP1）基因的双等位基因变异体相关，具体来说,影响其主动脉羧肽酶样蛋白（ACLP）亚型。我们描述了诊断为clEDS2的第15例患者（第13个家庭）。该患者的表型与已记录的病例明显相似，以及其他特征，如严重的早产和身材矮小。基于EDS测序面板的分析显示纯合AEBP1：NM_001129.5：c.2923del，p.Ala975Profs*22可能的致病变异，和母系遗传杂合COL11A1：NM_001854.4：c.1160A>G，我们患者的p.Lys387Arg变异具有不确定的意义。在对所有先前报告的clEDS2患者进行全面审查后，我们的患者表现出以下重叠表型，包括皮肤特征：过度扩张，萎缩性疤痕/伤口愈合延迟（100％），容易擦伤（100%），过度皮肤（93％）;骨骼特征：全身关节过度活动（93％），pesplanus（93%），脱位/半脱位（93％）；和心血管特征（86％）。我们的患者没有出现少数人报告的严重并发症的症状，包括肠系膜上动脉动脉瘤和破裂，主动脉根部动脉瘤/夹层,自发性气胸,和肠破裂。一起,该病例扩展了AEBP1相关cleDS2的遗传和临床表型谱。
