Anti-TCOF1 polyclonal antibody

Background. Treacher Collins syndrome (TCS) mainly presents with severe craniofacial developmental abnormalities characterized by a combination of bilateral downward-slanting palpebral fissures, colobotnas of the lower eyelids, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss. It is due to mutations in Treacher Collins syndrome 1 (TCOF1) (5q32-q33.1) and Polymerase RNA 1 polypeptides D and C (POLR1D [13q12.2], and POLR1 C [6p21.1]) genes, which are responsible for increased neuroepithelial apoptosis during embryogenesis resulting in the lack of neural crest cells involved in facial bone and cartilage formation. Altered function of the upper digestive tract has been reported, whereas severe dysmotility disorders have never been reported. We describe here the first case of TCS associated with histologically proven chronic intestinal pseudo -obstruction (CIPO) in humans. Case presentatios A 12-year-old boy with TCS due to TCOF1 gene deletion experienced nutritional difficulties and digestive intolerance from birth. CIPO was suspected during childhood because of severe intestinal dysmotility leading to enteral-jejunal nutrition intolerance and dependence on total parenteral nutrition. Diagnosis of CIPO with nervous abnormalities was histologically confirmed on a surgical rectal biopsy that showed enlarged ganglionic myenteric plexus. At the age of 9 years, an isolated colonic stenosis without dilatation responsible for severe abdominal pain and altered quality of life led to digestive derivation contributing to rapid disappearance of chronic abdominal pain. At the age of 12 years, the patient was still dependent on total home parenteral nutrition 7 days a week to maintain regular growth velocity. Conclusion. Recently, mice studies have pointed out the role played by TCOF1 in ganglionic cell migration in the foregut, suggesting that the synergistic haploinsufficiency of Tcof1 and Pax3, a transcription factor regulating the RET gene involved in disorders of neural crest cell development, probably results in colonic aganglionosis and may explain the association described here between TCS and CIPO. This case may correspond to this possible mechanism in humans. These findings and our clinical report suggest that CIPO may be assessed as unusual digestive manifestations in TCS with TCOF1 deletion. (C) 2017 Published by Elsevier Masson SAS.

Treacher Collins Syndrome (TCS) is the most common of the human mandibulofacial dysostosis disorders. Recently, a partial TCOF1 cDNA was identified and shown to contain mutations in TCS families, Here we present the entire exon/intron genomic structure and the complete coding sequence of TCOF1. TCOF1 encodes a low complexity protein of 1,411 amino acids, whose predicted protein structure reveals repeated motifs that mirror the organization of its exons. These motifs are shared with nucleolar trafficking proteins in other species and are predicted to be highly phosphorylated by casein kinase, Consistent with this, the full-length TCOF1 protein sequence also contains putative nuclear and nucleolar localization signals, Throughout the open reading frame, we detected an additional eight mutations in TCS families and several polymorphisms, We postulate that TCS results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development.