A Stop-gain Variant c.220C>T (p.(Gln74*)) in FLNB Segregates with Spondylocarpotarsal Synostosis Syndrome in a Consanguineous Family.

IF 2.5 3区 工程技术 Q2 BIOLOGY Yale Journal of Biology and Medicine Pub Date : 2023-09-29 eCollection Date: 2023-09-01 DOI:10.59249/UTCP9818
Hamna Shahid, Nazish Shakoor, Anisa Bibi, Asma Saleem Qazi, Rida Fatima Saeed, Aqeela Nawaz, Sajid Malik, Sara Mumtaz
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Abstract

Spondylocarpotarsal synostosis (SCT) syndrome is a very rare and severe form of skeletal dysplasia. The hallmark features of SCT are disproportionate short stature, scoliosis, fusion of carpal and tarsal bones, and clubfoot. Other common manifestations are cleft palate, conductive and sensorineural hearing loss, joint stiffness, and dental enamel hypoplasia. Homozygous variants in FLNB are known to cause SCT. This study was aimed to investigate the phenotypic and genetic basis of unique presentation of SCT syndrome segregating in a consanguineous Pakistani family. Three of the four affected siblings evaluated had severe short stature, short trunk, short neck, kyphoscoliosis, pectus carinatum, and winged scapula. The subjects had difficulty in walking and gait problems and complained of knee pain and backache. Roentgenographic examination of the eldest patient revealed gross anomalies in the axial skeleton including thoracolumbar and cervical fusion of ribs, severe kyphoscoliosis, thoracic and lumbar lordosis, coxa valga, fusion of certain carpals and tarsals, and clinodactyly. The patients had normal faces and lacked other typical features of SCT like cleft palate, conductive and sensorineural hearing loss, joint stiffness, and dental enamel hypoplasia. Whole exome sequencing (WES) of two affected siblings led to the discovery of a rare stop-gain variant c.220C>T (p.(Gln74*)) in exon 1 of the FLNB gene. The variant was homozygous and segregated with the malformation in this family. This study reports extensive phenotypic variability in SCT and expands the mutation spectrum of FLNB.

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FLNB中的一个停增变异株c.220C>T(p.(Gln74*))在一个血缘家族中分离并伴有强直性脊柱炎综合征。
强直性脊柱炎(SCT)综合征是一种非常罕见和严重的骨骼发育不良。SCT的标志性特征是不成比例的身材矮小、脊柱侧弯、腕骨和跗骨融合以及马蹄内翻足。其他常见表现为腭裂、传导性和感音神经性听力损失、关节僵硬和牙釉质发育不全。已知FLNB中的纯合变体会导致SCT。本研究旨在探讨在一个有血缘关系的巴基斯坦家庭中SCT综合征分离的独特表现的表型和遗传基础。在评估的四个受影响的兄弟姐妹中,有三个患有严重的身材矮小、躯干短、脖子短、后凸畸形、隆突和带翼肩胛骨。受试者有行走困难和步态问题,并抱怨膝盖疼痛和背痛。对年龄最大的患者进行的X线检查显示,轴骨出现严重异常,包括胸腰椎和颈椎肋骨融合、严重后凸、胸腰椎前凸、髋外翻、某些腕骨和跗骨融合以及斜指畸形。患者面部正常,缺乏其他典型的SCT特征,如腭裂、传导性和感音神经性听力损失、关节僵硬和牙釉质发育不全。两个受影响兄弟姐妹的全外显子组测序(WES)导致在FLNB基因的外显子1中发现了一种罕见的停止增益变体c.220C>T(p.(Gln74*))。该变体是纯合的,并与该家族的畸形分离。本研究报道了SCT的广泛表型变异,并扩展了FLNB的突变谱。
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来源期刊
Yale Journal of Biology and Medicine
Yale Journal of Biology and Medicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
5.00
自引率
0.00%
发文量
41
期刊介绍: The Yale Journal of Biology and Medicine (YJBM) is a graduate and medical student-run, peer-reviewed, open-access journal dedicated to the publication of original research articles, scientific reviews, articles on medical history, personal perspectives on medicine, policy analyses, case reports, and symposia related to biomedical matters. YJBM is published quarterly and aims to publish articles of interest to both physicians and scientists. YJBM is and has been an internationally distributed journal with a long history of landmark articles. Our contributors feature a notable list of philosophers, statesmen, scientists, and physicians, including Ernst Cassirer, Harvey Cushing, Rene Dubos, Edward Kennedy, Donald Seldin, and Jack Strominger. Our Editorial Board consists of students and faculty members from Yale School of Medicine and Yale University Graduate School of Arts & Sciences. All manuscripts submitted to YJBM are first evaluated on the basis of scientific quality, originality, appropriateness, contribution to the field, and style. Suitable manuscripts are then subject to rigorous, fair, and rapid peer review.
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