RT Journal Article
SR Electronic
T1 Impact of pathogenic <em>FBN1</em> variant types on the development of severe scoliosis in patients with Marfan syndrome
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 74
OP 80
DO 10.1136/jmedgenet-2021-108186
VO 60
IS 1
A1 Yuki Taniguchi
A1 Norifumi Takeda
A1 Ryo Inuzuka
A1 Yoshitaka Matsubayashi
A1 So Kato
A1 Toru Doi
A1 Hiroki Yagi
A1 Haruo Yamauchi
A1 Masahiko Ando
A1 Yasushi Oshima
A1 Sakae Tanaka
YR 2023
UL http://jmg.bmj.com/content/60/1/74.abstract
AB Background Among the several musculoskeletal manifestations in patients with Marfan syndrome, spinal deformity causes pain and respiratory impairment and is a great hindrance to patients’ daily activities. The present study elucidates the genetic risk factors for the development of severe scoliosis in patients with Marfan syndrome.Methods We retrospectively evaluated 278 patients with pathogenic or likely pathogenic FBN1 variants. The patients were divided into those with (n=57) or without (n=221) severe scoliosis. Severe scoliosis was defined as (1) patients undergoing surgery before 50 years of age or (2) patients with a Cobb angle exceeding 50° before 50 years of age. The variants were classified as protein-truncating variants (PTVs), which included variants creating premature termination codons and inframe exon-skipping, or non-PTVs, based on their location and predicted amino acid alterations, and the effect of the FBN1 genotype on the development of severe scoliosis was examined. The impact of location of FBN1 variants on the development of severe scoliosis was also investigated.Results Univariate and multivariate analyses revealed that female sex, PTVs of FBN1 and variants in the neonatal region (exons 25–33) were all independent significant predictive factors for the development of severe scoliosis. Furthermore, these factors were identified as predictors of progression of existing scoliosis into severe state.Conclusions We elucidated the genetic risk factors for the development of severe scoliosis in patients with Marfan syndrome. Patients harbouring pathogenic FBN1 variants with these genetic risk factors should be monitored carefully for scoliosis progression.Data are available upon reasonable request. All genetic data included in this study are provided in online supplemental table 1. Other data are available on reasonable request. Deidentified data are available on reasonable request subject to ethics approval from the corresponding author.