Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
Am J Med Genet A. 2023 Aug;191(8):2100-2112. doi: 10.1002/ajmg.a.63246. Epub 2023 May 14.
Biallelic variants in CHST3 gene result in congenital dislocation of large joints, club feet, short stature, rhizomelia, kypho-scoliosis, platyspondyly, epiphyseal dysplasia, flared metaphysis, in addition to minor cardiac lesions and hearing loss. Herein, we describe 14 new patients from 11 unrelated Egyptian families with CHST3-related skeletal dysplasia. All patients had spondyloepiphyseal changes that were progressive with age in addition to bifid distal ends of humeri which can be considered a diagnostic key in patients with CHST3 variants. They also shared peculiar facies with broad forehead, broad nasal tip, long philtrum and short neck. Rare unusual associated findings included microdontia, teeth spacing, delayed eruption, prominent angulation of the lumbar-sacral junction and atrial septal defect. Mutational analysis revealed 10 different homozygous CHST3 (NM_004273.5) variants including 7 missense, two frameshift and one nonsense variant. Of them, the c.384_391dup (p.Pro131Argfs*88) was recurrent in two families. Eight of these variants were not described before. Our study presents the largest series of patients with CHST3-related skeletal dysplasia from the same ethnic group. Furthermore, it reinforces that lethal cardiac involvement is a critical clinical finding of the disorder. Therefore, we believe that our study expands the phenotypic and mutational spectrum, and also highlights the importance of performing echocardiography in patients harboring CHST3 variants.
CHST3 基因的双等位基因突变导致先天性大关节脱位、马蹄内翻足、身材矮小、骨干发育不良、脊柱后凸侧凸、扁平椎、骨骺发育不良、干骺端增宽，此外还有轻微的心脏病变和听力损失。在此，我们描述了 11 个不相关的埃及家庭中的 14 名新的 CHST3 相关骨骼发育不良患者。所有患者均有脊柱骨骺改变，且随年龄增长逐渐进展，此外还存在肱骨远端分叉，这可作为 CHST3 变异患者的诊断关键。他们还具有相似的特殊面容，包括宽额头、宽鼻尖、长人中、短颈。罕见的不常见的相关表现包括小牙、牙齿间隙、出牙延迟、腰椎-骶骨交界处明显成角和房间隔缺损。突变分析显示 10 种不同的纯合 CHST3（NM_004273.5）变异，包括 7 种错义、2 种移码和 1 种无义变异。其中，c.384_391dup（p.Pro131Argfs*88）在两个家庭中反复出现。其中 8 种变异以前未被描述过。本研究展示了来自同一民族的最大 CHST3 相关骨骼发育不良患者系列。此外，它还证实了致命性心脏受累是该疾病的一个关键临床发现。因此，我们认为本研究扩展了表型和突变谱，并强调了在 CHST3 变异患者中进行超声心动图检查的重要性。
