19 Harley St, London, W1G 9QJ, UK
We are London's Top Spine Clinic

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

Icon for Elsevier Science Related Articles

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

Bone. 2019 Jan 16;:

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

BACKGROUND: NF-?B 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-?B). Animal studies suggest NEMO is required for NF-?B 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; ?-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-?B activity was quantitated in BM-MSCs using a luciferase NF-?B 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-?B activity was lower in BM-MSCs from IKBKG mutation carriers (n?=?5) compared to controls (3094?±?679 vs. 5422?±?1038/?g protein, p?0.01). However, no differences were identified on skeletal radiographics, aBMD, ?-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.

PMID: 30659980 [PubMed – as supplied by publisher]

Share to care...

Share on facebook
Share on twitter
Share on pinterest
Share on google
Share on linkedin
Share on skype

What we do...

The Harley Street Hospital


What is London spine unit and How it Works

The London Spine Unit was established in 2005 and has successfully treated over 5000 patients. All conditions are treated.

We treat all spinal disorders

The London Spine Unit specialises in Minimally Invasive Treatments allowing rapid recovery and return to normal function

Trusted by patients worldwide

The London Spine Unit provides the highest quality care to all patients and has VIP services for those seeking exceptional services

What our patients say about us ......