■痛风发育不良(GD)和Weill-Marchesani综合征(WMS)是两种罕见的遗传性疾病,被归类为肢端发育不良,并且在某些患者中具有许多临床和遗传重叠的共同特征。这两种疾病的特点是肢端特征,包括身材矮小,Brachydactyly,联合限制,和心脏受累。WMS与GD的区别主要在于眼部异常,包括高度近视,微球,扁豆异位,青光眼和缺乏危及生命的气道狭窄和早期致死率。这两种综合征是FBN1基因的等位基因疾病,与基因家族,包括具有血小板反应蛋白基序(ADAMTS)和潜在转化生长因子-β结合蛋白(LTBP)的解整合素和金属蛋白酶。尽管ADAMTSL2基因仅与肢端发育不良中的GD相关,有报道称ADAMTSL2相关GD患者表现出类似WMS的眼部异常.
■我们介绍了一位24岁的女性患者,扁豆异位,近视,身材矮小,接头刚度,厚皮肤,手脚短,和心脏瓣膜疾病与WMS一致。虚拟面板分析,包括WMS和GD相关基因,显示纯合c.493G>A(p。Ala165Thr)在ADAMTSL2基因中的变异体(NM_014694.4),以前曾在一名脑发育不良患者中报道过。
■越来越多的证据表明GD和WMS可能是ADAMTSL2基因的等位基因疾病。
UNASSIGNED: Geleophysic dysplasia (GD) and Weill-Marchesani syndrome (WMS) are two rare genetic disorders that are classified as acromelic dysplasias and have many common features that overlap clinically and genetically in some patients. Both diseases are characterized by acromelic features, including short stature, brachydactyly, joint limitations, and cardiac involvement. WMS is distinguished from GD mainly by ocular abnormalities, including high myopia,
microspherophakia, ectopia lentis, and glaucoma and the absence of the life-threatening airway stenosis and early lethality. These two syndromes are allelic diseases of the FBN1 gene, with the gene families including A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS) and latent transforming growth factor-beta-binding protein (LTBP). Although the ADAMTSL2 gene has been associated only with GD within the acromelic dysplasias, there have been reports of patients with ADAMTSL2-related GD exhibiting ocular abnormalities that resemble WMS.
UNASSIGNED: We present a 24-year-old female patient with
microspherophakia, ectopia lentis, myopia, short stature, joint stiffness, thick skin, short hands and feet, and cardiac valve disease consistent with WMS. The virtual panel analysis, including WMS and GD-related genes, revealed a homozygous c.493 G>A (p.Ala165Thr) variant in the ADAMTSL2 gene (NM_014694.4), which has been previously reported in a geleophysic dysplasia patient.
UNASSIGNED: Mounting evidence suggests that GD and WMS may be allelic diseases of the ADAMTSL2 gene.