Novel mutations of the SERPINF1 and FKBP10 genes in Chinese families with autosomal recessive osteogenesis imperfecta

Abstract

The aim of the present study was to characterize the clinical manifestations and identify the mutations of Serpin family F member 1 (SERPINF1) and FK506 binding protein 10 (FKBP10) genes in Chinese patients with osteogenesis imperfecta (OI). Using whole‑exome sequencing in the first and third probands, a novel mutation was identified in SERPINF1 and a novel compound heterozygous mutation was revealed in FKBP10. Using Sanger sequencing, an additional novel mutation in SERPINF1 was identified in a proband of family 2. In family 1, the proband presented with a novel homozygous missense mutation of the SERPINF1 gene, c.1067T>A (V356E). In family 2, the proband had a novel homozygous deletion mutation of the SERPINF1 gene, c.283+473_643+104del (p.Ala96_Gly215del). Serum pigment‑epithelium‑derived factor concentration was not detected in probands with OI type VI. For both families, the proband's father was demonstrated to have a heterozygous mutation of SERPINF1, whereas no mutations was detected in the probands' mothers. An assessment of allelic copy numbers revealed a deletion of SERPINF1 in the mother of family 1. The results of the present study demonstrate that patients may have mild symptoms of OI with a large fragment deletion in the SERPINF1 gene. Thus, the phenotype of Chinese patients with type VI OI is milder than that of Caucasian and Korean patients. In family 3, the proband displayed a novel compound heterozygous mutation in FKBP10, c.813_814delGA (p.Glu271AspfsX101) and c.831delC (p.Gly278AlafsX20), and did not have Bruck syndrome. Codon 831 of the FKBP10 gene may represent a mutation hotspot for human OI. These results extend both the phenotypic and the genotypic contents of OI patients with SERPINF1 or FKBP10 mutations.

Genotypic and Phenotypic Characteristics of 29 Patients With Rare Types of Osteogenesis Imperfecta: Average 5 Years of Follow-Up

“…Eighteen individuals (62.1%) with OI had IFITM5 gene mutations; LEPRE1, SEC24D, and SERPINF1 mutations were found in two cases (6.8, 6.8, and 6.8%, respectively). Other mutated genes included P4HB, PLS3, TMEM38B, WNT1, and FKBP10 (3.5, 3.5, 3.5, 3.5, and 3.5%, respectively), as previously described (Zhang et al, 2012(Zhang et al, , 2013(Zhang et al, , 2017(Zhang et al, , 2018Cao et al, 2019a,b).…”

“…The exome of probands, their parents, and siblings were sequenced to identify the pathogenic gene. As reported in our previous studies (Zhang et al, 2012(Zhang et al, , 2013(Zhang et al, , 2017(Zhang et al, , 2018Cao et al, 2019a,b), we designed a targeted gene sequencing panel for next-generation sequencing to economically and conveniently establish a comprehensive molecular diagnostic method for rare type OI and confirmed the possible mutations using Sanger sequencing.…”

“…The study population is composed of the 29 rare types of OI patients who were assessed at the Shanghai Jiao Tong University Affiliated Sixth People's Hospital between May 2005 and September 2020. Gene mutations in all patients were previously published in journals (Zhang et al, 2012(Zhang et al, , 2013(Zhang et al, , 2017(Zhang et al, , 2018Cao et al, 2019a,b). In addition, 185 Chinese probands of OI who carried mutations in the COL1A1 or COL1A2 genes have been reported in our studies (Xi et al, 2021).…”

“…In this study, we evaluated the mid-term clinical course of patients with rare types of OI (Zhang et al, 2012(Zhang et al, , 2013(Zhang et al, , 2017(Zhang et al, , 2018Cao et al, 2019a,b). The height, BMD, and fracture frequency of patients with or without bisphosphonates were 1 http://www.le.ac.uk/ge/collagen/ compared.…”

Understanding Musculoskeletal Disorders Through Next-Generation Sequencing

“…Recent studies using NGS techniques have discovered several novel and rare genetic variants involved in the pathogenesis of OI (Table IV). Novel candidate genes such as SERPINF1 101,102 , IFITM5, WNT1 103 , SEC24D, and P4HB 104 were identified by performing WES or targeted sequencing 105-109 . Several studies investigating patients with OI type V have identified mutations in the IFITM5 gene 110 .…”