Cushing proximal symphalangism and the NOG and GDF5 genes.
Proximal symphalangism (SYM1) is an autosomal-dominant developmental disorder of joint fusion. This disorder is best known from famous historical descriptions of two large kindred: Cushing's description in 1916 of the "straight-fingered" Brown family of Virginia and Drinkwater's description in 1917 of the British Talbot family of noble blood, descended from the English war hero John Talbot, the first Earl of Shrewsbury (1388-1453). Recent genetic studies link this phenotype to expression of abnormal genes at future joint sites: too little expression of NOG, a growth antagonist, or overexpression of GDF5, a growth agonist, results in cartilage overgrowth and bony fusion. This review unites in depth the first historical accounts of SYM1 with a clinical description and reviews the current understanding of the molecular mechanism underlying what is likely the oldest dominant trait ever studied.
Plett
Sara K
SK
College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Berdon
Walter E
WE
Cowles
Robert A
RA
Oklu
Rahmi
R
Campbell
John B
JB
D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D005384:Finger Joint / Q000002:abnormalities* / Q000000981:diagnostic imaging; D055428:Growth Differentiation Factor 5; D049673:History, 20th Century; D006801:Humans; D007592:Joint Diseases / Q000000981:diagnostic imaging / Q000235:genetics / Q000266:history*; D009154:Mutation; D010641:Phenotype; D011859:Radiography; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D055428:Growth Differentiation Factor 5; D000099176:Noggin Protein; C525893:GDF5 protein, human