Mutations in C2orf37, encoding a nucleolar protein, cause hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome.
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.
Alazami
Anas M
AM
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Al-Saif
Amr
A
Al-Semari
Abdulaziz
A
Bohlega
Saeed
S
Zlitni
Soumaya
S
Alzahrani
Fatema
F
Bavi
Prashant
P
Kaya
Namik
N
Colak
Dilek
D
Khalak
Hanif
H
Baltus
Andy
A
Peterlin
Borut
B
Danda
Sumita
S
Bhatia
Kailash P
KP
Schneider
Susanne A
SA
Sakati
Nadia
N
Walsh
Christopher A
CA
Al-Mohanna
Futwan
F
Meyer
Brian
B
Alkuraya
Fowzan S
FS
D000505:Alopecia / Q000235:genetics; D000595:Amino Acid Sequence; D001480:Basal Ganglia Diseases / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002889:Chromosomes, Human, Pair 2; D017124:Conserved Sequence; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D015894:Genome, Human; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D007006:Hypogonadism / Q000235:genetics; D008607:Intellectual Disability / Q000235:genetics; D008126:Lod Score; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016366:Open Reading Frames; D010375:Pedigree; D020161:Physical Chromosome Mapping; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D013577:Syndrome; D043743:Ubiquitin-Protein Ligase Complexes
C556016:DCAF17 protein, human; D009687:Nuclear Proteins; D043743:Ubiquitin-Protein Ligase Complexes