Mosaicism of a TCOF1 mutation in an individual clinically unaffected with Treacher Collins syndrome.
Treacher Collins syndrome (TCS) or mandibulofacial dysostosis is an autosomal dominant disorder of craniofacial development with 60% of its cases arising de novo. Other modes of inheritance such as autosomal recessive, gonadal mosaicism, and chromosomal rearrangement have also been proposed. This syndrome can result from TCOF1 gene mutations. In this study we identified a TCOF1 1408delAG heterozygous mutation in a patient with the clinical diagnosis of TCS. This same mutation was found in the clinically unaffected mother's leukocytes, hair root bulbs, buccal mucosa, urine, and stool. The mother has a clinically unaffected child and the maternal grandparents do not have the mutation. Because the mother has the mutation in cells derived from all three germ layers, we suspected the mutation was nonpenetrant. However, we could not detect the mutation in her skin fibroblasts, suggesting she is mosaic secondary to cell type specific selection.
Shoo
Brenda A
BA
Department of Pediatrics, Institute of Genetic Medicine, Center for Craniofacial Development and Disorders, The Johns Hopkins University, Baltimore, Maryland 21287-3914, USA.
McPherson
Elizabeth
E
Jabs
Ethylin Wang
EW
D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008342:Mandibulofacial Dysostosis / Q000175:diagnosis / Q000235:genetics*; D009030:Mosaicism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010750:Phosphoproteins / Q000235:genetics*
D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human