Achondroplasia

Achondroplasia (MIM 100800) Mutations in the gene encoding the fibroblast growth factor receptor 3... 

Achondroplasia (MIM 100800) and thanatophoric dysplasia (MIM 187600) Mutations In the gene encoding FGFR3. 

Thanatophoric (Gk thanatos "death" + pharos "bearing") dysplasia is the most common neonatal lethal skeletal dysplasia, displaying features similar to those of homozygous achondroplasia. 

The best-known of the chondrodysplasias is achondroplasia, the commonest cause of short-limbed dwarfism. Affected individuals have short limbs, nor-... 

Figure 48-15. Simplified scheme of the causation of achondroplasia (MIM 100800). In most cases studied so far, the mutation has been a G to A transition at nucleotide 1138. In a few cases, the mutation was a G to C transversion at the same nucleotide. This particular nucleotide is a real "hot spot" for mutation. Both mutations result in replacement of a Gly residue by an Arg residue in the transmembrane segment of the receptor. A few cases involving replacement of Gly by Cys at codon 375 have also been reported.

Scriver CR et al (editors) The Metabolic and Molecular Bases of Inherited Disease, 8th ed. McGraw-Hill, 2001 (This comprehensive four-volume text contains chapters on disorders of collagen biosynthesis and structure, Marfan syndrome, the mucopolysaccharidoses, achondroplasia, Alport syndrome, and craniosynostosis syndromes.)... 

Blindness (several forms) Deafness (several forms) Marfan syndrome Achondroplasia Neurofibromatosis Myotonic dystrophy Tuberous sclerosis All others... 

Sipila I, Kaitila I, Bland J, Veimo D, Muller J, Mohnike K, Neumeyer L, Ritzen M, Hagenas L. Growth hormone treatment in 35 prepubertal children with achondroplasia a five-year dose-response trial. Acta Paediatr... 

High High High Rare dominant Achondroplasia... 

Acanthosis nigricans, which is characterized by dark velvety thickening of the skin on the nape of the neck and in the groins and axillae, has been described in a non-obese 10-year-old boy with achondroplasia who received somatropin 3 lU/week for 7 years (54). 

Combined Failure of Antibody- and Cell-Mediated Immunity Severe combined immunodeficiency. Swiss and sex-linked types, death in infancy from fungal or viral infections Associated with thymoma, achondroplasia, or thrombocytopenia and eczema (Wiskott-Aldrich syndrome)... 

The primary mutation in achondroplasia results in a defect in internalization and degradation of the mutant receptor. Thus it is retained on the ceE surface and has uncontrolled and prolonged activation in chondrocytes. Hence, chondrocyte maturation and terminal differentiation are inhibited. Following the discovery of the association between achondroplasia and FGFR3 mutations, other similar gain-of-function mutations at other sites within this gene have been identified as the cause of less common forms of dwarfism, including thanatophoric dysplasia types I and n and hypochondroplasia. ... 

Bellus GA, Hefferon TW, Ortiz de Luna RI, Hecht JT, Horton WA, Machado M, et al. Achondroplasia is defined by recurrent G380R mutations of FGFR3. 

Francomano CA, Ortiz de Luna RI, Hefferon TW, BeUus GA, Turner CE, Taylor E, et al. Localization of the achondroplasia gene to the distal 2.5 Mb of... 

Gooding HC, Boehm K, Thompson RE, Hadley D, Francomano CA, Biesecker BB. Issues surrounding prenatal genetic testing for achondroplasia. Prenatal Diag 2002 22 933-40. 

Sykes B. Germfine and somatic mosaicism in achondroplasia. J Med Genet 2000 37 956-8. 

Horton WA> Lunstrum GP. Fibroblast growth factor receptor 3 mutations in achondroplasia and related forms of dwarfism. Rev Endo Metab Dis 2002 3 381-5. 

Nelson FW, Hecht JT, Horton WA, Butler IJ, Goldie WD, Miner M. Neurological basis of respiratory complications in achondroplasia. Ann Neurol 1988 24 89-93. 

Pauh RM> Horton VK, Glinski LP, Reiser CA. Prospective assessment of risks for cervicomedullary-j unction compression in infants with achondroplasia. Am J Hum Genet 1995 56 732-44. 

Sliiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, et al. Mutations in the trans-membrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 1994 78 335-42. 

Tiemann-Boege I, Navidid W, Grewal R, Cohn D, Eskenaz B, Wyrobek AJ, et al. The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect. Proc Nad Acad Sci USA 2002 99 14952-57. 

Velinov M, Slaugenhaupt SA, Stoilov I, Scott Cl, Gusella JF, Tsipouras P. The gene for achondroplasia maps to the telomeric region of chromosome 4p. Nat Genet 1994 6 314-7. 

Bellus GA, Mack ML, et al. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Am J Hmn Genet 1998 63 711-6. 

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