Alopecia, neurological defects, and endocrinopathy syndrome caused by decreased expression of RBM28, a nucleolar protein associated with ribosome biogenesis.
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.
Nousbeck
Janna
J
Laboratory of Molecular Dermatology, Department of Dermatology, Rambam Health Care Campus, 31096 Haifa, Israel.
Spiegel
Ronen
R
Ishida-Yamamoto
Akemi
A
Indelman
Margarita
M
Shani-Adir
Ayelet
A
Adir
Noam
N
Lipkin
Ehud
E
Bercovici
Sivan
S
Geiger
Dan
D
van Steensel
Maurice A
MA
Steijlen
Peter M
PM
Bergman
Reuven
R
Bindereif
Albrecht
A
Choder
Mordechai
M
Shalev
Stavit
S
Sprecher
Eli
E
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
D009687:Nuclear Proteins; C530063:RBM28 protein, human; D016601:RNA-Binding Proteins