PT  - JOURNAL ARTICLE
AU  - Yuki Taniguchi
AU  - Norifumi Takeda
AU  - Ryo Inuzuka
AU  - Yoshitaka Matsubayashi
AU  - So Kato
AU  - Toru Doi
AU  - Hiroki Yagi
AU  - Haruo Yamauchi
AU  - Masahiko Ando
AU  - Yasushi Oshima
AU  - Sakae Tanaka
TI  - Impact of pathogenic <em>FBN1</em> variant types on the development of severe scoliosis in patients with Marfan syndrome
AID  - 10.1136/jmedgenet-2021-108186
DP  - 2021 Dec 16
TA  - Journal of Medical Genetics
PG  - jmedgenet-2021-108186
4099  - http://jmg.bmj.com/content/early/2021/12/15/jmedgenet-2021-108186.short
4100  - http://jmg.bmj.com/content/early/2021/12/15/jmedgenet-2021-108186.full
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.