Molecular Confirmation of G1138A Mutation in FGFR gene in Achondroplasia

  • Shyam Bahadur Khanal Central Department of Biotechnology, Tribhuvan University.
  • Mitesh Shrestha Nepal Academy of Science and Technology, Khumaltar, Lalitpur, Nepal.
  • Hemanta Kumari Chaudhary Center for Molecular Dynamics- Nepal, Swaraj Sadan, Prasutigriha Marg, Thapathali-11, Kathmandu, Nepal
  • Smita Shrestha Central Department of Biotechnology, Tribhuvan University, Kirtipur, Kathmandu, Nepal
  • Rohit Kumar Pokharel Institute of Medicine, Maharajgunj Medicine Campus, Tribhuvan University, Maharajgunj, Kathmandu, Nepal
Keywords: achondroplasia; dwarfism; fibroblast growth factor receptor 3 (FGFR3); point Mutation.


Introduction: Achondroplasia (ACH) is the most common form of skeletal dysplasia of genetic origin in humans which is characterized by disproportionate rhizomelic dwarfism. Heterozygous mutation in the transmembrane domain of the FGFR3 gene (4p16.3) occurs as a de novo mutation in most of the cases.

 Methods: DNA was isolated from seven samples, out of which, five had clinical features of Achondroplasia while one was dwarf but did not show symptoms of the disorder and one as negative control. PCR was performed for the region incorporating the hotspot region viz. 1138th nucleotide. PCR amplicon of size 164 bp was obtained from all the samples, and was sequenced.

Results: Sequence analysis showed the presence of mutation (G to A transition) in all of the five samples. The five samples that showed the clinical features of Achondroplasia had mutation in the region being analyzed while the single patient who had no clinical manifestations of the disorder despite being dwarf had no such mutation. Among the five patients studied, one patient had a family history of Achondroplasia as observed through pedigree analysis while the remaining four cases were sporadic in nature.

 Conclusions: This study further supports that the G1138A mutation is the one of the most common point mutation among Achondroplasia cases. Genetic diagnosis can be useful to identify the disease prenatally and differentiate other life threatening dwarfism for the safety of both mother and fetus.

 Keywords: achondroplasia; dwarfism; fibroblast growth factor receptor 3 (FGFR3); point Mutation.


1. Ornitz DM, Marie PJ. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes & development. 2002 Jun 15;16(12):1446-65.[PubMed]
2. Su N, Du X, Chen L. FGF signaling: its role in bone development and human skeleton diseases. Front Biosci. 2008 Jan 1; 13:2842-65. [PubMed]
3. Wang H, Sun Y, Wu W, Wei X, Lan Z, Xie J. A novel missense mutation of FGFR3 in a Chinese female and her fetus with Hypochondroplasia by next-generation sequencing. Clinica chimica acta. 2013 Aug 23; 423:62-5. [Full Text]
4. Foldynova‐Trantirkova S, Wilcox WR, Krejci P. Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias. Human mutation. 2012 Jan 1; 33(1):29-41. [PubMed]
5. Pokharel RK, Alimsardjono H, Fukushima Y, Fukushima T, Shiba R, & Matsuo M. Highly recurrent G1138A mutation of fibroblast growth factor receptor 3 (FGFR3) gene identified in achondroplasia, the commonest form of chondroplasia. J Nepal Med Assoc. 1997; 35:52-57.
6. Hung CC, Lee CN, Chang CH, Jong YJ, Chen CP, Hsieh WS, Su YN, Lin WL. Genotyping of the G1138A mutation of the FGFR3 gene in patients with achondroplasia using high-resolution melting analysis. Clinical biochemistry. 2008 Feb 1; 41(3):162-6. [DOI]
7. He X, Xie F, Ren ZR. Rapid detection of G1138A and G1138C mutations of the FGFR3 gene in patients with achondroplasia using high-resolution melting analysis. Genetic testing and molecular biomarkers. 2012 Apr 1; 16(4):297-301. [Full Text]
8. Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, Winokur ST, Wasmuth JJ. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell. 1994 Jul 29; 78(2):335-42. [PubMed]
9. Neumann L, Kunze J, Uhl M, Stöver B, Zabel B, Spranger J. Survival to adulthood and dominant inheritance of platyspondylic skeletal dysplasia, Torrance-Luton type. Pediatric radiology. 2003 Nov 1; 33(11):786-90. [PubMed]
10. Peek MJ, Devonald KJ, Beilby R, EllwoodJ D. The value of routine early pregnancy ultrasound in the antenatal booking clinic. Australian and New Zealand journal of obstetrics and gynaecology. 1994 May 1; 34(2):140-3. [Full Text]
11. Rousseau F, Bonaventure J, Legeai-Mallet L, Pelet A, Rozet JM, Maroteaux P, Le Merrer M, Munnich A. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature. 1994 Sep; 371(6494):252. [PubMed]
12. Wang Y, Liu Z, Liu Z, Zhao H, Zhou X, Cui Y, Han J. Advances in research on and diagnosis and treatment of achondroplasia in China. Intractable & rare diseases research. 2013 May 31; 2(2):45-50. [PubMed]
How to Cite
Khanal, S., Shrestha, M., Chaudhary, H., Shrestha, S., & Pokharel, R. (2018). Molecular Confirmation of G1138A Mutation in FGFR gene in Achondroplasia. Journal of Nepal Medical Association, 56(211), 683-686.
Original Article