Yu Meiyan, Liu Xiaomei, Ran Ni, Yang Zhaochuan, Shan Yanchun
Department of Child Health Care, the Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Mar 10;41(3):271-277. doi: 10.3760/cma.j.cn511734-20221212-00865.
To retrospectively analyze the clinical and genetic characteristics of six patients with Acromicric dysplasia due to variants of the FBN1 gene.
Six patients who had visited the Affiliated Hospital of Qingdao University between February 2018 and October 2020 were selected as the study subjects. Clinical data of the patients were collected. High-throughput sequencing was carried out. And candidate variants were verified by Sanger sequencing.
All of the six patients had presented with severe short stature (< 3s), brachydactyly, short and broad hands and feet. Other manifestations included joint stiffness, facial dysmorphism, delayed bone age, liver enlargement, coracoid femoral head, and lumbar lordosis. Genetic testing revealed that all had harbored heterozygous variants of the FBN1 gene. Patient 1 had harbored a c.5183C>T (p.A1728V) missense variant in exon 42, which had derived from his father (patient 2). Patient 3 had harbored a c.5284G>A (p.G1762S) missense variant in exon 43, which had derived from her mother (patient 4). Patient 5 had harbored a c.5156G>T (p.C1719F) missense variant in exon 42, which was de novo in origin. Patient 6 had harbored a c.5272G>T (p.D1758Y) missense variant in exon 43, which was also de novo in origin. The variants carried by patients 1, 3 and 6 were known to be pathogenic. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the FBN1: c.5156G>T was rated as a pathogenic variant (PS2+PM1+PM2_Supporting +PM5+PP3).
All of the six patients had severe short stature and a variety of other clinical manifestations, which may be attributed to the variants of the FBN1 gene.
回顾性分析6例因FBN1基因变异导致的肢端短小发育不全患者的临床和遗传特征。
选取2018年2月至2020年10月期间就诊于青岛大学附属医院的6例患者作为研究对象。收集患者的临床资料。进行高通量测序。并通过Sanger测序验证候选变异。
6例患者均表现为严重身材矮小（<3s）、短指畸形、手足短而宽。其他表现包括关节僵硬、面部畸形、骨龄延迟、肝脏肿大、喙突股骨头和腰椎前凸。基因检测显示，所有患者均携带FBN1基因的杂合变异。患者1在第42外显子中携带一个c.5183C>T（p.A1728V）错义变异，该变异来自他的父亲（患者2）。患者3在第43外显子中携带一个c.5284G>A（p.G1762S）错义变异，该变异来自她的母亲（患者4）。患者5在第42外显子中携带一个c.5156G>T（p.C1719F）错义变异，该变异为新发。患者6在第43外显子中携带一个c.5272G>T（p.D1758Y）错义变异，该变异也为新发。已知患者1、3和6携带的变异具有致病性。根据美国医学遗传学与基因组学学会（ACMG）的指南，FBN1:c.5156G>T被评为致病性变异（PS2+PM1+PM2_支持+PM5+PP3）。
6例患者均有严重身材矮小及多种其他临床表现，可能归因于FBN1基因变异。
