当前位置： SCI文献检索 > BONE期刊下所有文献 > Absence of an osteopetrosis phenotype in IKBKG (NEMO) mutation-positive women: A case-control study.

Absence of an osteopetrosis phenotype in IKBKG (NEMO) mutation-positive women: A case-control study.

Abstract：

BACKGROUND:NF-κB essential modulator (NEMO), encoded by IKBKG, is necessary for activation of the ubiquitous transcription factor nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Animal studies suggest NEMO is required for NF-κB mediated bone homeostasis, but this has not been thoroughly studied in humans. IKBKG loss-of-function mutation causes incontinentia pigmenti (IP), a rare X-linked disease featuring linear hypopigmentation, alopecia, hypodontia, and immunodeficiency. Single case reports describe osteopetrosis (OPT) in boys carrying hypomorphic IKBKG mutations. METHOD:We studied the bone phenotype in women with IP with evaluation of radiographs of the spine and non-dominant arm and leg; lumbar spine and femoral neck aBMD using DXA; μ-CT and histomorphometry of trans-iliac crest biopsy specimens; bone turnover markers; and cellular phenotype in bone marrow skeletal (stromal) stem cells (BM-MSCs) in a cross-sectional, age-, sex-, and BMI-matched case-control study. X-chromosome inactivation was measured in blood leucocytes and BM-MSCs using a PCR method with methylation of HpaII sites. NF-κB activity was quantitated in BM-MSCs using a luciferase NF-κB reporter assay. RESULTS:Seven Caucasian women with IP (age: 24-67 years and BMI: 20.0-35.2 kg/m2) and IKBKG mutation (del exon 4-10 (n = 4); c.460C>T (n = 3)) were compared to matched controls. The IKBKG mutation carriers had extremely skewed X-inactivation (>90:10%) in blood, but not in BM-MSCs. NF-κB activity was lower in BM-MSCs from IKBKG mutation carriers (n = 5) compared to controls (3094 ± 679 vs. 5422 ± 1038/μg protein, p < 0.01). However, no differences were identified on skeletal radiographics, aBMD, μ-architecture of the iliac crest, or bone turnover markers. The IKBKG mutation carriers had a 1.7-fold greater extent of eroded surfaces relative to osteoid surfaces (p < 0.01), and a 2.0-fold greater proportion of arrested reversal surface relative to active reversal surface (p < 0.01). CONCLUSION:Unlike mutation-positive males, the IKBKG mutation-positive women did not manifest OPT.

journal_name

Bone

journal_title

Bone

authors

Frost M,Tencerova M,Andreasen CM,Andersen TL,Ejersted C,Svaneby D,Qui W,Kassem M,Zarei A,McAlister WH,Veis DJ,Whyte MP,Frederiksen AL

doi

10.1016/j.bone.2019.01.014

subject

Has Abstract

pub_date

2019-04-01 00:00:00

pages

243-254

eissn

8756-3282

issn

1873-2763

pii

S8756-3282(19)30015-8

journal_volume

121

pub_type

杂志文章

在线工具

Absence of an osteopetrosis phenotype in IKBKG (NEMO) mutation-positive women: A case-control study.