Oligodontia is caused by mutation in LTBP3, the gene encoding latent TGF-beta binding protein 3.
We have identified a consanguineous Pakistani family where oligodontia is inherited along with short stature in an autosomal-recessive fashion. Increased bone density was present in the spine and at the base of the skull. Using high-density single-nucleotide polymorphism microarrays for homozygosity mapping, we identified a 28 Mb homozygous stretch shared between affected individuals on chromosome 11q13. Screening selected candidate genes within this region, we identified a homozygous nonsense mutation, Y774X, within LTBP3, the gene for the latent TGF-beta binding protein 3, an extracellular matrix protein believed to be required for osteoclast function.
Noor
Abdul
A
Neuropsychiatry and Development Lab, Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, ON M5T 1R8, Canada.
Windpassinger
Christian
C
Vitcu
Irina
I
Orlic
Marija
M
Rafiq
Muhammad Arshad
MA
Khalid
Mahwish
M
Malik
Mahmood Nasir
MN
Ayub
Muhammad
M
Alman
Benjamin
B
Vincent
John B
JB
D000848:Anodontia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D001827:Body Height / Q000235:genetics; D015519:Bone Density / Q000235:genetics; D001846:Bone Development / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D018389:Codon, Nonsense; D003241:Consanguinity; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010154:Pakistan; D010375:Pedigree; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D018389:Codon, Nonsense; D017931:DNA Primers; C509038:LTBP3 protein, human; D053779:Latent TGF-beta Binding Proteins; D012333:RNA, Messenger