Overview
Gene (OMIM No.) |
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Function of gene/protein |
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Clinical phenotype (OMIM phenotype no.) | |
Inheritance |
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Ocular features |
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Systemic features | Alagille syndrome
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Key investigations |
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Molecular diagnosis | Next generation sequencing
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Management |
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Therapies under research |
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Further information |
Additional information
There is no specific genotype-phenotype relationship in Alagille syndrome but mutations causing Hajdu-Cheney syndrome are all localised to exon 34 on the NOTCH2 gene in germline cells.[5-9] NOTCH2 mutations in somatic cells can cause splenic marginal zone lymphoma.[12]
References
- Hajdu n, kauntze r. Cranio-skeletal dysplasia. Br J Radiol. 1948;21(241):42-48. doi:10.1259/0007-1285-21-241-42
- Alagille D, Odièvre M, Gautier M, Dommergues JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr. 1975;86(1):63-71. doi:10.1016/s0022-3476(75)80706-2
- Larsson C, Lardelli M, White I, Lendahl U. The human NOTCH1, 2, and 3 genes are located at chromosome positions 9q34, 1p13-p11, and 19p13.2-p13.1 in regions of neoplasia-associated translocation. Genomics. 1994;24(2):253-258. doi:10.1006/geno.1994.1613
- McDaniell R, Warthen DM, Sanchez-Lara PA, et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet. 2006;79(1):169-173. doi:10.1086/505332
- Spinner NB, Gilbert MA, Loomes KM, Krantz ID. Alagille Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; May 19, 2000
- Simpson MA, Irving MD, Asilmaz E, et al. Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat Genet. 2011;43(4):303-305. Published 2011 Mar 6. doi:10.1038/ng.779
- Majewski J, Schwartzentruber JA, Caqueret A, et al. Mutations in NOTCH2 in families with Hajdu-Cheney syndrome. Hum Mutat. 2011;32(10):1114-1117
- Isidor B, Lindenbaum P, Pichon O, et al. Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis. Nat Genet. 2011;43(4):306-308
- Gray MJ, Kim CA, Bertola DR, et al. Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu-Cheney syndrome. Eur J Hum Genet. 2012;20(1):122-124
- Canalis E, Zanotti S. Hajdu-Cheney syndrome: a review. Orphanet J Rare Dis. 2014;9:200
- Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137(2):216-233. doi:10.1016/j.cell.2009.03.045
- Kiel MJ, Velusamy T, Betz BL, et al. Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J Exp Med. 2012;209(9):1553-1565
- Swan L, Gole G, Sabesan V, Cardinal J, Coman D. Congenital Glaucoma: a Novel Ocular Manifestation of Hajdu-Cheney Syndrome. Case Rep Genet. 2018;2018:2508345. Published 2018 Oct 21. doi:10.1155/2018/2508345
- Rennie CA, Chowdhury S, Khan J, et al. The prevalence and associated features of posterior embryotoxon in the general ophthalmic clinic. Eye (Lond). 2005;19(4):396-399. doi:10.1038/sj.eye.6701508
- Gasch AT, Janjani A, Weber M, Garland DL, Chan CC. Ocular pathology and lens analysis in Hajdu-Cheney syndrome. Ann Ophthalmol. 2001;33(2):141-144. doi:10.1007/s12009-001-0011-3