Identification and in vivo functional characterization of novel compound heterozygous BMP1 variants in osteogenesis imperfecta.
Osteogenesis imperfecta (OI) comprises a heterogeneous group of disorders that are characterized by susceptibility to bone fractures, and range in severity from a subtle increase in fracture frequency to death in the perinatal period. Most patients have defects in type I collagen biosynthesis with autosomal-dominant inheritance, but many autosomal-recessive genes have been reported. We applied whole-exome sequencing to identify mutations in a Korean OI patient who had an umbilical hernia, frequent fractures, a markedly short stature, delayed motor development, scoliosis, and dislocation of the radial head, with a bowed radius and ulna. We identified two novel variants in the BMP1 gene: c.808A>G and c.1297G>T. The former variant caused a missense change p.(Met270Val) and the latter variant caused the skipping of exon 10. The hypofunctional nature of the two variants was demonstrated in a zebrafish assay.
Department of Pediatrics, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Sung Yoon
SY
Cho
P V
PV
Asharani
Ok-Hwa
OH
Kim
Aritoshi
A
Iida
Noriko
N
Miyake
Naomichi
N
Matsumoto
Gen
G
Nishimura
Chang-Seok
CS
Ki
Geehay
G
Hong
Su Jin
SJ
Kim
Young Bae
YB
Sohn
Sung Won
SW
Park
Jieun
J
Lee
Younghee
Y
Kwun
Thomas J
TJ
Carney
Rimm
R
Huh
Shiro
S
Ikegawa
Dong-Kyu
DK
Jin
D019943:Amino Acid Substitution; D000818:Animals; D055395:Bone Morphogenetic Protein 1 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D007223:Infant; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015027:Zebrafish
C525705:BMP1 protein, human; D055395:Bone Morphogenetic Protein 1
BMP1; mutation; osteogenesis imperfecta; whole-exome sequencing; zebrafish