Unknown

Dataset Information

0

Impact on bone of an estrogen receptor-alpha gene loss of function mutation.


ABSTRACT: CONTEXT: The kindred described is the only known instance of a germ line loss of function mutation of estrogen receptor (ER)-alpha. OBJECTIVE: Our objective was to assess the impact of a loss of function mutation in the ER-alpha gene on histomorphometry, bone volumetric density, bone geometry and skeletal growth, and ER-alpha heterozygosity on spine density and adult height in an extended pedigree. DESIGN AND PARTICIPANTS: A longitudinal follow-up of the propositus with homozygous loss of function mutation of ER-alpha and single contact evaluation of the kindred were performed. MAIN OUTCOME MEASURES: Iliac crest bone biopsy and peripheral quantitative computed tomography of propositus with serial measures of areal spine bone mineral density (aBMD) by dual-energy x-ray absorptiometry and bone age were performed. Members of pedigree were evaluated for ER-alpha mutation carrier status and spine aBMD. RESULTS: Bone biopsy revealed marked osteopenia (cortex: 641 microm), low trabecular volume (10.6%), decreased thickness (76.2 microm), normal trabecular number, and low activation frequency (0.099/yr). Radial periosteal circumference was similar, endosteal circumference larger, and trabecular and cortical volumetric bone mineral density markedly lower (158 and 1092 mg/cm(3), respectively) than controls. Spine aBMD at age 28.5 yr (0.745 g/cm(2)) decreased to 0.684 g/cm(2) (Z score -3.85) in 3.5 yr. Bone age advanced from 15-17.5 yr. Kindred analysis revealed that gene carriers had spine aBMD Z scores less than zero (P = 0.003), but carriers and nonmutant members were similar (-0.84 +/- 0.26 vs. -0.64 +/- 0.16). CONCLUSION: Homozygous ER-alpha disruption markedly affects bone growth, mineral content, and structure but not periosteal circumference. ER-alpha heterozygosity appears to not impair spine aBMD.

SUBMITTER: Smith EP 

PROVIDER: S-EPMC2729204 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Impact on bone of an estrogen receptor-alpha gene loss of function mutation.

Smith Eric P EP   Specker Bonny B   Bachrach Bert E BE   Kimbro K S KS   Li X J XJ   Young Marian F MF   Fedarko Neal S NS   Abuzzahab M J MJ   Frank Graeme R GR   Cohen Robert M RM   Lubahn Dennis B DB   Korach Kenneth S KS  

The Journal of clinical endocrinology and metabolism 20080527 8


<h4>Context</h4>The kindred described is the only known instance of a germ line loss of function mutation of estrogen receptor (ER)-alpha.<h4>Objective</h4>Our objective was to assess the impact of a loss of function mutation in the ER-alpha gene on histomorphometry, bone volumetric density, bone geometry and skeletal growth, and ER-alpha heterozygosity on spine density and adult height in an extended pedigree.<h4>Design and participants</h4>A longitudinal follow-up of the propositus with homozy  ...[more]

Similar Datasets

| S-EPMC6889517 | biostudies-literature
| S-EPMC3169108 | biostudies-literature
| S-EPMC2698732 | biostudies-literature
| S-EPMC6379583 | biostudies-literature
| S-EPMC2887492 | biostudies-literature
2016-11-22 | GSE51535 | GEO
| S-EPMC7957950 | biostudies-literature
| S-EPMC1736016 | biostudies-other
| S-EPMC3180739 | biostudies-literature
| S-EPMC5413105 | biostudies-literature