Clinical hypochondroplasia in a family caused by a heterozygous double mutation in FGFR3 encoding GLY380LYS

American Journal of Medical Genetics, Part A

Volumn 143, Issue 4, 2007, Pages 355-359

  Santos, Heloísa G ^a   Almeida, Maria ^a,d   Fernandes, Helena ^b   Wilkie, Andrew ^c  

^a Edificio Egas Moniz   (Portugal)

^b HOSPITAL CENTRAL DO FUNCHAL   (Portugal)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d Egas Moniz University   (Portugal)

Author keywords

Achondroplasia; Bone dysplasia; Double mutation; FGFR3; Hypochondroplasia

Indexed keywords

ARGININE; GLYCINE; LYSINE;

ADULT; AGED; AMINO ACID SUBSTITUTION; ARTICLE; CASE REPORT; CAUSAL ATTRIBUTION; CLINICAL FEATURE; EXON; FEMALE; FGFR2 GENE; FGFR3 GENE; GENE FUNCTION; GENE MUTATION; GENETIC ASSOCIATION; GENOTYPE PHENOTYPE CORRELATION; HETEROZYGOTE; HUMAN; HYPOCHONDROPLASIA; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; RECEPTOR GENE; SEQUENCE ANALYSIS; SIGNAL TRANSDUCTION; SPERMATOGONIUM;

ACHONDROPLASIA; ADULT; AGED; AMINO ACID SUBSTITUTION; BASE SEQUENCE; CODON; FEMALE; GLYCINE; HUMANS; LYSINE; MOLECULAR SEQUENCE DATA; MUTATION; PHENOTYPE; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 3; SEQUENCE ANALYSIS, DNA; SKULL;

EID: 33846818796     PISSN: 15524825     EISSN: 15524833     Source Type: Journal    
DOI: 10.1002/ajmg.a.31556     Document Type: Article

References (24)

1. Bellus G, Hefferon T, Ortiz de Luna R, Hecht JT, Horton WA, Machado M, Kaitila I, McIntosh I, Francomano CA. 1995a. Achondroplasia is defined by recurrent G380R mutations in FGFR3. Am J Hum Genet 56:368-373.
2. Bellus G, McIntosh I, Smith EA, Aylsworth AS, Kaitile I, Horton WA, Greenhaw GA, Hecht JT, Francomano CA. 1995b. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nat Genet 10:357-359.
3. Bellus G, Spector EB, Speiser PW, Weaver CA, Garber AT, Bryke CR, Israel J, Rosengren SS, Webster MK, Donoghue DJ, Francomano CA. 2000. Distinct missense mutations in the FGFR3 Lys 650 codon modulate receptor kinase activation and the severity of skeletal dysplasia phenotype. Am J Hum Genet 67:1411-1421.
4. Bonaventure J, Rousseau F, Legeai Mallet L, Le Merrer M, Munnich A, Maroteaux P. 1996. Common mutations in the fibroblast growth factor receptor 3 (FGFR3) gene account for achondroplasia, hypochondroplasia and thanatophoric dwarfism. Am J Med Genet 63:148-154.
5. Francomano CA, Ortiz de Luna RI, Hefferon TW, Bellus GA, Turner CE, Taylor E, Meyers DA, Blanton SH, Murray JC, McIntosh I. 1994. Localization of the achondroplasia gene to the distal 2.5 Mb of human chromosome 4p. Hum Mol Genet 3:787-792.
6. Goriely A, McVean GAT, Rojmyr M, Ingemarsson B, Wilkie AOM. 2003. Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. Science 301:643-646.
7. Goriely A, McVean GAT, van Pelt AMM, O'Rourke AW, Wall SA, de Rooij DG, Wilkie AOM. 2005. Gain-of-function amino acid substitutions drive positive selection of FGFR2 mutations in human spermatogonia. Proc Natl Acad Sci USA 102:6051-6056.
8. Horton WA. 2006. Recent milestones in achondroplasia research. Am J Med Genet Part A 140A:166-169.
9. Kondrashov AS. 2002. Direct estimates of human per nucleotide mutation rates at 20 loci causing mendelian diseases. Hum Mutat 21:12-27.
10. Le Merrer M, Rousseau F, Legeai-Mallet L, Landais JC, Pelet A, Bonaventure J, Sanak M, Weissenbach J, Stoll C, Munnich A. 1994. A gene for achondroplasia - Hypochondroplasia maps to chromosome 4p. Nat Genet 6:318-321.
11. Passos-Bueno MR, Wilcox WR, Jabs EW, Sertié AL, Alonso LG, Kitoh H. 1999. Clinical spectrum of fibroblast growth factor receptor mutations. Hum Mutat 14:115-119.
12. Prinos P, Costa T, Sommer A, Kilpatrick MW, Tsipouras P. 1995. A common FGFR3 mutation in achondroplasia. Hum Mol Genet 4:2097-2101.
13. Prinster C, Carrera P, Del Maschio M, Weber G, Maghnie M, Vigone Mc, Mora S, Tonini G, Rigon F, Belluffi G, Severi F, Chiumelo G, Ferrari M. 1998. Comparison of clinical - Radiological and molecular findings in hypochondroplasia. Am J Med Genet 75:109-112.
14. Raffioni S, Zhu Ya-Zhen, Bradshaw RA, Thompson LM. 1998. Effect of transmembrane and kinase domain mutations on fibroblast growth factor receptor 3 chimera signalling in PC12 cells. J Biol Chem 273:35250-35259.
15. Rannan-Eliya SV, Taylor IB, Marieke I, de Heer IM, van den Ouweland AM, Wall SA, Wilkie AOM. 2004. Paternal origin of FGFR3 mutations in Muenke-type craniosynostosis. Hum Genet 115:200-207.
16. Robertson SC, Tynan JA, Donoghue DJ. 2000. RTK mutations and human syndromes: When good receptors turn bad. Trends Genet 16:265-271.
17. Rousseau F, Bonaventure J, Legeal-Mallet L, Pelet A, Rozet J-M, Maroreaux P, Le Merrer M, Munnich A. 1994. Mutations in the gene encoding fibroblast growth factor receptor 3 in achondroplasia. Nature 371:252-254.
18. Rump P, Letteboer TGW, Gille JJP, Torringa MJL, Baerts W, Van Gestel JPJ, Verheij JBGM, Van Hessen AJ. 2006. Severe complications in a child with cchondroplasia and two FGFR3 mutations on the same allele. Am J Med Genet Part A 140A:284-290.
19. Savov A, Angelicheva D, Balassopoulou A, Jordanova A, Noussia-Arvanitakis SN, Kalaydjeva L. 1995. Double mutant alleles: Are they rare? Hum Mol Genet 7:1169-1171.
20. Shiang R, Thompson LM, Zhu Y-Z, Church DM, Fielder TJ, Bocian M, Winokur AT, Wasmuth JJ. 1994. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell 78:335-342.
21. Vajo Z, Francomano CA, Wilkin DJ. 2000. The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: The achondroplasia family of skeletal dysplasias, muenke craniosynostosis, and Crouzon syndrome with Acanthosis Nigricans. Endocr Rev 21:23-29.
22. Velinov M, Slaugenhaupt SA, Stoilov I, Scott CI Jr, Gusella JF, Tsipouras P. 1994. The gene for achondroplasia maps to the telomeric region of chromosome 4p. Nat Genet 6:314-317.
23. Webster MK, Donoghue DJ. 1996. Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia. EMBO J 15:520-527.
24. Wilkie AOM. 2005. Bad bones, absent smell, selfish testes: The pleiotropic consequences of human FGF receptor mutations. Cytokine Growth Factor Rev 16:187-203.