FBN1 gene mutation in a Chinese pedigree of mild Geleophysic dysplasia type 2/Acromicric dysplasia and the exploration of growth-promoting therapy
10.3760/cma.j.cn311282-20220914-00531
- VernacularTitle:FBN1基因杂合突变导致轻型Geleophysic发育不良2型/Acromicric发育不良中国家系及促生长治疗的探讨
- Author:
Mengtian HUANG
1
;
Qiuli CHEN
;
Huamei MA
;
Yanhong LI
;
Jun ZHANG
;
Song GUO
Author Information
1. 中山大学附属第一医院儿科，广州 510080
- Keywords:
FBN1 gene;
Geleophysic dysplasia;
Acromicric dysplasia;
Acromelic dysplasia;
Short stature;
Therapy
- From:
Chinese Journal of Endocrinology and Metabolism
2023;39(6):492-498
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To summarize the clinical and genetic features of 7 patients with a mild form of Geleophysic dysplasia type 2(GD2)/Acromicric dysplasia(AD) induced by fibrillin 1(FBN1) gene mutation from one Chinese family.Methods:A Chinese pedigree of mild GD2/AD treated at the Pediatric Endocrinology Department at the First Affiliated Hospital of Sun Yat-sen University between August 2017 and May 2022 was collected. Whole-exome genetic sequencing of the FBN1 gene were performed to establish the diagnosis. Additionally, a literature review was further conducted.Results:In this family, among 13 individuals spanning three generations, there were 7 affected cases, including 1 adult female, 1 adult male, and 5 children. All individuals exhibited postnatal growth failure, severe disproportionate short stature, and lacked typical facial features. Exome sequencing and Sanger sequencing confirmed the presence of a heterozygous missense mutation c. 5099A>G(p.Tyr1700Cys) in exon 42 of the FBNI gene in 6 affected individuals(Ⅱ-1, Ⅲ-1 to Ⅲ-5), which was identified as a pathogenic mutation. This mutation was previously reported in a Chinese classical achondroplasia(AD) family. Based on comprehensive genetic analysis, clinical features, and multisystem evaluation, 3 cases were diagnosed with mild type 2 growth hormone deficiency(GD2), and 4 cases were diagnosed with mild AD. Recombinant human growth hormone(rhGH; 1.1-1.4 IU·kg -1·week -1) was applied to all the 5 children, and additional gonadotropin releasing hormone analogue(GnRHa) was administered to the 2 girls in late puberty, resulting in certain growth-promoting effect. Conclusions:The c. 5099A>G(p.Tyr1700Cys) mutation not only leads to the classical type of achondroplasia(AD) as reported in the literature but also causes the non-classical GD2 or AD(mild GD2/AD). Further research is warranted to investigate the long-term therapeutic effects of rhGH treatment.
