A Review of Three Chinese Cases of Acromicric/Geleophysic Dysplasia with FBN1 Mutations

Abstract

Objective: This study aims to explore the clinical features and molecular diagnosis of FBN1-related acromelic dysplasia in Chinese patients. Methods: The clinical and genetic features of three FBN1-related acromicric dysplasia (AD)/geleophysic dysplasia (GD) Chinese patients from two families were reviewed, and comprehensive medical evaluations were performed. Targeted next-generation sequencing was used to detect genetic mutations associated with short statures, including FBN1. Sanger sequencing was used to determine the de novo mutation origin. Results: Patient 1 presented with short stature, short and stubby hands and feet, mild facial dysmorphism, hepatomegaly, delayed bone age and beak-like femoral heads. Patient 2 and this patient's father merely presented with short stature, wide and short hands, and beak-like femoral heads. One novel mutation, c.5272G>T(p.D1758Y), and one known mutation, c.5183C>T(p.A1728V), were identified in these patients. Conclusion:The clinical features varied among these patients. The variant c.5272G>T(p. D1758Y) is a novel mutation.

Case Report: Two different acromelic dysplasia phenotypes in a Chinese family caused by a missense mutation in FBN1 and a literature review

“…Taking “ FBN1 ” AND “acromelic dysplasia” in English or Chinese as the keywords, literature was searched at PubMed, CNKI, and Wanfang up to April 2024. The combination of the cases we identified and previous case reports corresponded to 7 FBN1 variants that contributed to different phenotypes of acromelic dysplasia ( 1 , 2 , 4 , 5 , 7 – 18 ). All genetic and phenotypic data are summarized in Table 1 .…”

“…Acromelic dysplasia caused by fibrillin 1 ( FBN1 ) gene mutation is an autosomal dominant disorder, consisting of acromicric dysplasia (AD, OMIM #102370), geleophysic dysplasia 2 (GD2, OMIM #614185), and Weill-Marchesani syndrome 2 (WMS2, OMIM #608328) ( 1 ). AD, with an approximate prevalence of <1 in 1,000,000, is a rare skeletal dysplasia characterized by severe short stature, small hands and feet, stiff joints, thickened skin, and progressive dwarfism with normal birth length and intelligence ( 2 ).…”

Acromicric dysplasia caused by a mutation of fibrillin 1 in a family: A case report

“…In the 2015 revision of the classification of hereditary bone diseases, acral dysplasia included 10 diseases, among which the FBN1 gene mutation causes AD, GD, and WMS, and specific mutations in the FBN1 gene have been found in AD, GD and WMS patients[ 1 , 4 , 12 ]. The FBN1 gene is located in the long arm of human chromosome 15 (15q15–q21.1) and contains 66 exons, encoding a 2871-aa (350 kDa) structural protein called fibrillin (FBN)1[ 13 ]. FBN1 consists of 47 epidermal growth factor-like domains and seven transforming growth factor (TGF)-β1-binding-protein-like domains[ 14 ].…”

“…Physical examination showed that the hands were wide and short, but there was no joint stiffness, and there were no abnormality in cardiovascular, abdominal or endocrine examination. The X-ray examination showed that the tubular bone of the hands were shortened and the femoral head was beaked[ 13 ]. Although these cases had the same gene mutation site, the clinical phenotypes varied.…”

Pathogenic variants affecting the TB5 domain of the fibrillin-1 protein: not only in geleophysic/acromicric dysplasias but also in Marfan syndrome

“…hotspot for GPHYSD/ACMICD [15][16][17][18][19][20][21][22][23] variants in the FBN1 gene. Indeed, 28 different heterozygous pathogenic variants were reported in patients, all within the TB5 motif encoded by exons 41 and 42.…”