A mutation in the heparin-binding site of noggin as a novel mechanism of proximal symphalangism and conductive hearing loss

• Published in: Biochemical and biophysical research communications Vol. 447; no. 3; pp. 496 - 502
• Main Authors: Masuda, Sawako, Namba, Kazunori, Mutai, Hideki, Usui, Satoko, Miyanaga, Yuko, Kaneko, Hiroki, Matsunaga, Tatsuo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.05.2014
• Subjects: Amino Acid Sequence; Amino Acid Substitution - genetics; Arginine - chemistry; Arginine - genetics; Asian Continental Ancestry Group - genetics; Binding Sites - genetics; BMP; Bone Morphogenetic Protein 7 - metabolism; Carrier Proteins - chemistry; Carrier Proteins - genetics; Carrier Proteins - metabolism; Child; Conductive hearing loss; Crystallography, X-Ray; Cysteine - chemistry; Cysteine - genetics; Docking simulation; Female; Finger Joint - abnormalities; Hearing Loss, Conductive - genetics; Heparin; Heparin - metabolism; Heterozygote; Humans; Japan; Joint Diseases - congenital; Joint Diseases - genetics; Molecular Sequence Data; Mutation, Missense; NOG; Pedigree; Signal Transduction; Symphalangism; Japan; HSPG; Docking simulation; BMP; DPOAE; TCS; NOG; DIP; Symphalangism; Conductive hearing loss; SYM1; ABR; CT; BMPR; TCC; PIP; Heparin; SYNS1

•Nog with novel heterozygous p.R136C mutation was identified in patients with SYM1.•The noggin mutant was simulated to have reduced binding affinity to heparin.•Change in noggin–heparin interaction is suggested to underlie the clinical features. The access of bone morphogenetic protein (BMP) to the...