title: Abnormal vertebral segmentation and the notch signaling pathway in man.
abstract: Abnormal vertebral segmentation (AVS) in man is a relatively common congenital malformation but cannot be subjected to the scientific analysis that is applied in animal models. Nevertheless, some spectacular advances in the cell biology and molecular genetics of somitogenesis in animal models have proved to be directly relevant to human disease. Some advances in our understanding have come through DNA linkage analysis in families demonstrating a clustering of AVS cases, as well as adopting a candidate gene approach. Only rarely do AVS phenotypes follow clear Mendelian inheritance, but three genes-DLL3, MESP2, and LNFG-have now been identified for spondylocostal dysostosis (SCD). SCD is characterized by extensive hemivertebrae, trunkal shortening, and abnormally aligned ribs with points of fusion. In familial cases clearly following a Mendelian pattern, autosomal recessive inheritance is more common than autosomal dominant and the genes identified are functional within the Notch signaling pathway. Other genes within the pathway cause diverse phenotypes such as Alagille syndrome (AGS) and CADASIL, conditions that may have their origin in defective vasculogenesis. Here, we deal mainly with SCD and AGS, and present a new classification system for AVS phenotypes, for which, hitherto, the terminology has been inconsistent and confusing.
authors.affiliation: Clinical Genetics, Royal Devon & Exeter Hospital, and Peninsula Medical School, Exeter, United Kingdom. peter.turnpenny@rdeft.nhs.uk
authors.forename: Peter D
authors.initials: PD
authors.lastname: Turnpenny
authors.forename: Ben
authors.initials: B
authors.lastname: Alman
authors.forename: Alberto S
authors.initials: AS
authors.lastname: Cornier
authors.forename: Philip F
authors.initials: PF
authors.lastname: Giampietro
authors.forename: Amaka
authors.initials: A
authors.lastname: Offiah
authors.forename: Olivier
authors.initials: O
authors.lastname: Tassy
authors.forename: Olivier
authors.initials: O
authors.lastname: Pourquié
authors.forename: Kenro
authors.initials: K
authors.lastname: Kusumi
authors.forename: Sally
authors.initials: S
authors.lastname: Dunwoodie
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D004413:Dysostoses / Q000145:classification / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010641:Phenotype; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013131:Spine / Q000002:abnormalities* / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism
chemical_list: D051880:Receptors, Notch