Mutations causing Greenberg dysplasia but not Pelger anomaly uncouple enzymatic from structural functions of a nuclear membrane protein

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Mutations causing Greenberg dysplasia but not Pelger anomaly uncouple enzymatic from structural functions of a nuclear membrane protein.

The lamin B receptor (LBR) is an inner nuclear membrane protein with a structural function interacting with chromatin and lamins, and an enzymatic function as a sterol reductase. Heterozygous LBR mutations cause nuclear hyposegmentation in neutrophils (Pelger anomaly), while homozygous mutations cause prenatal death with skeletal defects and abnormal sterol metabolism (Greenberg dysplasia). It ...

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Pelger-Huët anomaly and Greenberg skeletal dysplasia: LBR-associated diseases of cholesterol metabolism

Lamin B Receptor (LBR) is an inner nuclear membrane protein associated with the rare human diseases Pelger-Huët anomaly and Greenberg skeletal dysplasia. A new study has used CRISPR/Cas9-mediated genetic manipulations in a human cell system to determine that the molecular etiology of these previously poorly understood disorders is a defect in cholesterol synthesis due to loss of LBR-associated ...

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The Lamin B receptor is essential for cholesterol synthesis and perturbed by disease-causing mutations

Lamin B receptor (LBR) is a polytopic membrane protein residing in the inner nuclear membrane in association with the nuclear lamina. We demonstrate that human LBR is essential for cholesterol synthesis. LBR mutant derivatives implicated in Greenberg skeletal dysplasia or Pelger-Huët anomaly fail to rescue the cholesterol auxotrophy of a LBR-deficient human cell line, consistent with a loss-of-...

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Inherited Disorder: Pelger-Huët Anomaly

Submit Manuscript | http://medcraveonline.com Abbreviations: AML: Acute Myeloid Leukemia; CBC: Complete Blood Count; CML: Chronic Myeloid Leukemia; HIV: Human Immunodeficiency Virus; IFN-g: Interferon Gamma; INM: Inner Nuclear Membrane; LBR: Lamin B Receptor; MDS: Myelodysplastic Syndrome; NE: Nuclear Envelope; ONM: Outer Nuclear Membrane; PHA: Pelger-Huët Anomaly; PHA: PseudoPelger-Huët Anomal...

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Congenital abnormalities reported in Pelger-Huët homozygosity as compared to Greenberg/HEM dysplasia: highly variable expression of allelic phenotypes.

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ژورنال

عنوان ژورنال: Nucleus

سال: 2010

ISSN: 1949-1034,1949-1042

DOI: 10.4161/nucl.1.4.12435