| Structural highlights
Disease
NOGG_HUMAN Defects in NOG are a cause of symphalangism proximal syndrome (SYM1) [MIM:185800. SYM1 is characterized by the hereditary absence of the proximal interphalangeal (PIP) joints (Cushing symphalangism). Severity of PIP joint involvement diminishes towards the radial side. Distal interphalangeal joints are less frequently involved and metacarpophalangeal joints are rarely affected whereas carpal bone malformation and fusion are common. In the lower extremities, tarsal bone coalition is common. Conducive hearing loss is seen and is due to fusion of the stapes to the petrous part of the temporal bone.[1] [2] [3] [4] Defects in NOG are the cause of multiple synostoses syndrome type 1 (SYNS1) [MIM:186500; also known as synostoses, multiple, with brachydactyly/symphalangism-brachydactyly syndrome. SYNS1 is characterized by tubular-shaped (hemicylindrical) nose with lack of alar flare, otosclerotic deafness, and multiple progressive joint fusions commencing in the hand. The joint fusions are progressive, commencing in the fifth proximal interphalangeal joint in early childhood (or at birth in some individuals) and progressing in an ulnar-to-radial and proximal-to-distal direction. With increasing age, ankylosis of other joints, including the cervical vertebrae, hips, and humeroradial joints, develop.[5] Defects in NOG are the cause of tarsal-carpal coalition syndrome (TCC) [MIM:186570. TCC is an autosomal dominant disorder characterized by fusion of the carpals, tarsals and phalanges, short first metacarpals causing brachydactyly, and humeroradial fusion. TCC is allelic to SYM1, and different mutations in NOG can result in either TCC or SYM1 in different families.[6] Defects in NOG are a cause of stapes ankylosis with broad thumb and toes (SABTS) [MIM:184460; also known as Teunissen-Cremers syndrome. SABTS is a congenital autosomal dominant disorder that includes hyperopia, a hemicylindrical nose, broad thumbs, great toes, and other minor skeletal anomalies but lacked carpal and tarsal fusion and symphalangism.[7] Defects in NOG are the cause of brachydactyly type B2 (BDB2) [MIM:611377. BDB2 is a subtype of brachydactyly characterized by hypoplasia/aplasia of distal phalanges in combination with distal symphalangism, fusion of carpal/tarsal bones, and partial cutaneous syndactyly.[8]
Function
NOGG_HUMAN Essential for cartilage morphogenesis and joint formation. Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite.[9]
See Also
References
- ↑ Gong Y, Krakow D, Marcelino J, Wilkin D, Chitayat D, Babul-Hirji R, Hudgins L, Cremers CW, Cremers FP, Brunner HG, Reinker K, Rimoin DL, Cohn DH, Goodman FR, Reardon W, Patton M, Francomano CA, Warman ML. Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis. Nat Genet. 1999 Mar;21(3):302-4. PMID:10080184 doi:10.1038/6821
- ↑ Takahashi T, Takahashi I, Komatsu M, Sawaishi Y, Higashi K, Nishimura G, Saito H, Takada G. Mutations of the NOG gene in individuals with proximal symphalangism and multiple synostosis syndrome. Clin Genet. 2001 Dec;60(6):447-51. PMID:11846737
- ↑ Mangino M, Flex E, Digilio MC, Giannotti A, Dallapiccola B. Identification of a novel NOG gene mutation (P35S) in an Italian family with symphalangism. Hum Mutat. 2002 Mar;19(3):308. PMID:11857750 doi:10.1002/humu.9016
- ↑ van den Ende JJ, Mattelaer P, Declau F, Vanhoenacker F, Claes J, Van Hul E, Baten E. The facio-audio-symphalangism syndrome in a four generation family with a nonsense mutation in the NOG-gene. Clin Dysmorphol. 2005 Apr;14(2):73-80. PMID:15770128
- ↑ Rudnik-Schoneborn S, Takahashi T, Busse S, Schmidt T, Senderek J, Eggermann T, Zerres K. Facioaudiosymphalangism syndrome and growth acceleration associated with a heterozygous NOG mutation. Am J Med Genet A. 2010 Jun;152A(6):1540-4. doi: 10.1002/ajmg.a.33387. PMID:20503332 doi:10.1002/ajmg.a.33387
- ↑ Dixon ME, Armstrong P, Stevens DB, Bamshad M. Identical mutations in NOG can cause either tarsal/carpal coalition syndrome or proximal symphalangism. Genet Med. 2001 Sep-Oct;3(5):349-53. PMID:11545688 doi:10.109700125817-200109000-00004
- ↑ Brown DJ, Kim TB, Petty EM, Downs CA, Martin DM, Strouse PJ, Moroi SE, Milunsky JM, Lesperance MM. Autosomal dominant stapes ankylosis with broad thumbs and toes, hyperopia, and skeletal anomalies is caused by heterozygous nonsense and frameshift mutations in NOG, the gene encoding noggin. Am J Hum Genet. 2002 Sep;71(3):618-24. Epub 2002 Jun 27. PMID:12089654 doi:10.1086/342067
- ↑ Lehmann K, Seemann P, Silan F, Goecke TO, Irgang S, Kjaer KW, Kjaergaard S, Mahoney MJ, Morlot S, Reissner C, Kerr B, Wilkie AO, Mundlos S. A new subtype of brachydactyly type B caused by point mutations in the bone morphogenetic protein antagonist NOGGIN. Am J Hum Genet. 2007 Aug;81(2):388-96. Epub 2007 Jun 8. PMID:17668388 doi:10.1086/519697
- ↑ Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Belmonte JC, Choe S. Structural basis of BMP signalling inhibition by the cystine knot protein Noggin. Nature. 2002 Dec 12;420(6916):636-42. PMID:12478285 doi:10.1038/nature01245
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