Analyses of clinical features and mechanism of skeletal dysplasia in patients with NANS mutations.

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K20898
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Masunaga Yohei 浜松医科大学, 医学部, 特任助教 (20907795)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: NANS / NANS-CDG / SEMD / 脊椎骨端骨幹端異形

Outline of Final Research Achievements

We revealed in the patients with N-acetylneuraminic acid synthetase-congenital disorder of glycosylation (NANS-CDG) that (1) growth failure in patients with NANS-CDG become severe after birth; (2) NANS plays an important role in postnatal growth and fetal brain development; (3) spondyloepimetaphyseal dysplasia (SEMD) is recognizable at birth and shows remarkable postnatal evolution; (4) NANS-CDG is associated with low-normal serum sialic acid, obviously elevated urine N-acetylmannosamine, and normal N- and O-glycosylation of serum proteins; and (5) NANS-CDG is divided into classic Camera-Genevieve type and more severe Faye-Peterson type. Furthermore, we also revealed that impaired proliferation of chondrocyte may contribute to the pathogenesis of growth retardation and SEMD in patients with NANS-CDG.

Free Research Field

内分泌

Academic Significance and Societal Importance of the Research Achievements

シアル酸合成酵素の異常を原因とするN-acetylneuraminic acid synthetase-congenital disorder of glycosylation (NANS-CDG)は非常に稀な疾患であるため、臨床像や発症機序は未解明な点が多い。われわれはNANS-CDG患者3例の臨床および遺伝学的所見を詳細に検討し、NANS-CDG患者の新たな臨床的特徴を明らかにした。また、軟骨由来細胞株を用いた機能解析により、脊椎骨端骨幹端異形成・成長障害の発症機序には軟骨細胞の増殖障害が関与する可能性があることを明らかにした。