Mutations in C2orf37, Encoding a Nucleolar Protein, Cause Hypogonadism, Alopecia, Diabetes Mellitus, Mental Retardation, and Extrapyramidal Syndrome

• Published in: American journal of human genetics Vol. 83; no. 6; pp. 684 - 691
• Main Authors: Alazami, Anas M., Al-Saif, Amr, Al-Semari, Abdulaziz, Bohlega, Saeed, Zlitni, Soumaya, Alzahrani, Fatema, Bavi, Prashant, Kaya, Namik, Colak, Dilek, Khalak, Hanif, Baltus, Andy, Peterlin, Borut, Danda, Sumita, Bhatia, Kailash P., Schneider, Susanne A., Sakati, Nadia, Walsh, Christopher A., Al-Mohanna, Futwan, Meyer, Brian, Alkuraya, Fowzan S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.12.2008; Cell Press; Elsevier
• Subjects: Alopecia - genetics; Amino Acid Sequence; Basal Ganglia Diseases - genetics; Base Sequence - genetics; Cells; Chromosomes, Human, Pair 2; Conserved Sequence; Diabetes Mellitus - genetics; Female; Genes; Genes, Recessive; Genetic Linkage; Genome, Human; Genotype & phenotype; Haplotypes; Homozygote; Humans; Hypogonadism - genetics; Intellectual Disability - genetics; Lod Score; Male; Medical disorders; Molecular Sequence Data; Mutation; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Open Reading Frames; Pedigree; Physical Chromosome Mapping; Proteins; Sequence Analysis, DNA; Sequence Deletion; Syndrome; Ubiquitin-Protein Ligase Complexes; Saudi Arabia
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1016/j.ajhg.2008.10.018

Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome (also referenced as Woodhouse-Sakati syndrome) is a rare autosomal recessive multisystemic disorder. We have identified a founder mutation consisting of a single base-pair deletion in C2orf37 in eight families of Saudi origin. Three other loss-of-function mutations were subsequently discovered in patients of different ethnicities. The gene encodes a nucleolar protein of unknown function, and the cellular phenotype observed in patient lymphoblasts implicates a role for the nucleolus in the pathogenesis of this disease. Our findings expand the list of human disorders linked to the nucleolus and further highlight the developmental and/or maintenance functions of this organelle.