Abstract
Single-gene disorders offer unique opportunities to shed light upon fundamental physiological processes in humans. We investigated an autosomal-recessive phenotype characterized by alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome). By using homozygosity mapping and candidate-gene analysis, we identified a loss-of-function mutation in RBM28, encoding a nucleolar protein. RBM28 yeast ortholog, Nop4p, was previously found to regulate ribosome biogenesis. Accordingly, electron microscopy revealed marked ribosome depletion and structural abnormalities of the rough endoplasmic reticulum in patient cells, ascribing ANE syndrome to the restricted group of inherited disorders associated with ribosomal dysfunction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Alopecia / genetics*
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Alopecia / metabolism
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Alopecia / pathology
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Amino Acid Sequence
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Cell Nucleolus / metabolism
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Cells, Cultured
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Endocrine System Diseases / genetics*
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Endocrine System Diseases / metabolism
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Endocrine System Diseases / pathology
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Endoplasmic Reticulum / metabolism
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Endoplasmic Reticulum / ultrastructure
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Female
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Genetic Predisposition to Disease*
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Humans
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Male
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Molecular Sequence Data
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Nervous System Diseases / genetics*
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Nervous System Diseases / metabolism
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Nervous System Diseases / pathology
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism
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Pedigree
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Polymorphism, Single Nucleotide
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism
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Ribosomes / metabolism
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Ribosomes / ultrastructure
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Syndrome
Substances
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Nuclear Proteins
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RBM28 protein, human
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RNA-Binding Proteins