Clinical and molecular delineation of spondylocostal dysostosis type 3

Abstract

F IGURE 1 T2-weighted (A), T1-weighted (B,C) MRI images and 3D-CT-reconstruction (D) images of the affected individual. Severe segmentation defects of vertebrae of thoracic and lumbar spine with hemivertebrae, butterfly vertebrae and solitary pelvic kidney. Whole spine reconstruction showing severe kyphoscoliosis with dysplastic spine and rib anomalies (rib fusion, dysplasia, aplasia of 9th or 10th rib). (E) Schematic representation of LFNG gene and localization of published mutations in patients with SCDO3. The variant described in this study is located in exon 2 of LFNG (NM_001040167.1) and highlighted in gray. (F,G) Effect of the p. (Thr149Ile) variant on the LFNG structure. (F) Structure of wild type LFNG in ribbon presentation. Thr149 (T149) and the adjacent His126 (H126) are shown in space-filled presentation. A green arrow marks a stabilizing side chain hydrogen bond between both residues. (G) Structure of the p. (Thr149Ile) (T149I) variant, which lacks the side chain hydrogen bond. Instead, an unfavorable steric overlap is observed (indicated by a red arrow). CT, computed tomography; MRI, magnetic resonance imaging [Colour figure can be viewed at wileyonlinelibrary.com] To the Editor, Spondylocostal dysostosis (SCDO) is a heterogeneous group of rare spine disorders defined by multiple vertebral segmentation defects (M-SDV) and rib anomalies. Patients with SCDO present with short trunk short stature and mild to significant scoliosis. Severely reduced thorax size and a loss of natural thoracic kyphosis might lead to respiratory insufficiency in some affected individuals. Seven subtypes are differentiated based on the affected gene, including SCDO3 Received: 21 December 2020 Revised: 26 February 2021 Accepted: 27 February 2021