Ann Lab Med.  2013 Mar;33(2):150-152. 10.3343/alm.2013.33.2.150.

Identification of a GDF5 Mutation in a Korean Patient with Brachydactyly Type C without Foot Involvement

• Seo SH
• Park MJ
• Kim SH
• Kim OH
• Park S
• Cho SI
• Park SS
• Seong MW

• KMID: 1781317
• DOI: http://doi.org/10.3343/alm.2013.33.2.150

Abstract

Brachydactyly type C (BDC) is characterized by shortening of the middle phalanges of the index, middle, and little fingers. Hyperphalangy of the index and middle finger and shortening of the first metacarpal can also be observed. BDC is a rare genetic condition associated with the GDF5 gene, and this condition has not been confirmed by genetic analysis so far in the Korean population. Herein, we present a case of a 6-yr-old girl diagnosed with BDC confirmed by molecular genetic analysis. The patient presented with shortening of the second and third digits of both hands. Sequence analysis of the GDF5 gene was performed and the pathogenic mutation, c.1312C>T (p.Arg438Cys), was identified. Interestingly, this mutation was previously described in a patient who presented with the absence of the middle phalanges in the second through fifth toes. However, our patient showed no involvement of the feet. Considering intrafamilial and interfamilial variability, molecular analysis of isolated brachydactyly is warranted to elucidate the genetic origin and establish a diagnosis.

Keyword

Brachydactyly; GDF5 gene; Mutational analysis

MeSH Terms

Asian Continental Ancestry Group/*genetics
Brachydactyly/diagnosis/*genetics
Child
DNA Mutational Analysis
Female
Fingers/anatomy & histology
Growth Differentiation Factor 5/*genetics
Humans
Mutation
Republic of Korea
Growth Differentiation Factor 5

Figure

• 

  Fig. 1 Radiographic findings of both hands at age 5 yr and 7 months. The bilateral short first metacarpals show large pseudoepiphyses. The middle phalanges of the second, third, and fifth fingers are short, with clinodactyly of the fifth fingers. The fourth fingers are unaffected. The proximal phalanges of both third fingers are short. Note the segmentation anomaly with accessory ossification along the proximal phalanx and an accessory ivory dense epiphysis at the base of the distal phalanx of the left third finger. Note the ulnar deviation of the left second finger and radial curvature of the third finger. The carpal bone age is retarded.Abbreviations: Rt, right; Lt, left.

• 

  Fig. 2 Sequence analysis of the GDF5 gene. A heterozygous mutation of c.1312C>T in exon 2 is noted.

Reference

1. Temtamy SA. Brachydactyly. Orphanet J Rare Dis. 2008; 3:15. PMID: 18554391.

2. Schwabe GC, Türkmen S, Leschik G, Palanduz S, Stöver B, Goecke TO, et al. Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1. Am J Med Genet A. 2004; 124A:356–363. PMID: 14735582.

3. Seemann P, Schwappacher R, Kjaer KW, Krakow D, Lehmann K, Dawson K, et al. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. J Clin Invest. 2005; 115:2373–2381. PMID: 16127465.

4. Savarirayan R, White SM, Goodman FR, Graham JM Jr, Delatycki MB, Lachman RS, et al. Broad phenotypic spectrum caused by an identical heterozygous CDMP-1 mutation in three unrelated families. Am J Med Genet A. 2003; 117A:136–142. PMID: 12567410.

5. Baek GH, Chung MS, Park YB, Yoo KH. The relative incidence of congenital anomalies of the hand. J Korean Orthop Assoc. 1997; 32:796–801.

6. Everman DB, Bartels CF, Yang Y, Yanamandra N, Goodman FR, Mendoza-Londono JR, et al. The mutational spectrum of brachydactyly type C. Am J Med Genet. 2002; 112:291–296. PMID: 12357473.

7. Polinkovsky A, Robin NH, Thomas JT, Irons M, Lynn A, Goodman FR, et al. Mutations in CDMP1 cause autosomal dominant brachydactyly type C. Nat Genet. 1997; 17:18–19. PMID: 9288091.

8. Holder-Espinasse M, Escande F, Mayrargue E, Dieux-Coeslier A, Fron D, Doual-Bisser A, et al. Angel shaped phalangeal dysplasia, hip dysplasia, and positional teeth abnormalities are part of the brachydactyly C spectrum associated with CDMP-1 mutations. J Med Genet. 2004; 41:e78. PMID: 15173244.

9. Yang W, Cao L, Liu W, Jiang L, Sun M, Zhang D, et al. Novel point mutations in GDF5 associated with two distinct limb malformations in Chinese: brachydactyly type C and proximal symphalangism. J Hum Genet. 2008; 53:368–374. PMID: 18283415.

10. Dawson K, Seeman P, Sebald E, King L, Edwards M, Williams J 3rd, et al. GDF5 is a second locus for multiple-synostosis syndrome. Am J Hum Genet. 2006; 78:708–712. PMID: 16532400.

11. Byrnes AM, Racacho L, Nikkel SM, Xiao F, MacDonald H, Underhill TM, et al. Mutations in GDF5 presenting as semidominant brachydactyly A1. Hum Mutat. 2010; 31:1155–1162. PMID: 20683927.