title: Alopecia, neurological defects, and endocrinopathy syndrome caused by decreased expression of RBM28, a nucleolar protein associated with ribosome biogenesis.
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.
authors.affiliation: Laboratory of Molecular Dermatology, Department of Dermatology, Rambam Health Care Campus, 31096 Haifa, Israel.
authors.forename: Janna
authors.initials: J
authors.lastname: Nousbeck
authors.forename: Ronen
authors.initials: R
authors.lastname: Spiegel
authors.forename: Akemi
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.forename: Margarita
authors.initials: M
authors.lastname: Indelman
authors.forename: Ayelet
authors.initials: A
authors.lastname: Shani-Adir
authors.forename: Noam
authors.initials: N
authors.lastname: Adir
authors.forename: Ehud
authors.initials: E
authors.lastname: Lipkin
authors.forename: Sivan
authors.initials: S
authors.lastname: Bercovici
authors.forename: Dan
authors.initials: D
authors.lastname: Geiger
authors.forename: Maurice A
authors.initials: MA
authors.lastname: van Steensel
authors.forename: Peter M
authors.initials: PM
authors.lastname: Steijlen
authors.forename: Reuven
authors.initials: R
authors.lastname: Bergman
authors.forename: Albrecht
authors.initials: A
authors.lastname: Bindereif
authors.forename: Mordechai
authors.initials: M
authors.lastname: Choder
authors.forename: Stavit
authors.initials: S
authors.lastname: Shalev
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
mesh_terms: D000328:Adult; D000505:Alopecia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D002466:Cell Nucleolus / Q000378:metabolism; D002478:Cells, Cultured; D004700:Endocrine System Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009422:Nervous System Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism / Q000648:ultrastructure; D013577:Syndrome
chemical_list: D009687:Nuclear Proteins; C530063:RBM28 protein, human; D016601:RNA-Binding Proteins