We identified and characterized a Chinese family with autosomal dominant Brachydactyly type B1 (BDB1). Linkage analysis revealed that the disease gene of the Chinese BDB1 family was linked to ROR2 locus. Mutational hot spot of ROR2 gene was amplified by polymerase chain reaction (PCR) and sequenced directly. A c.2265C>A heterozygous mutation was detected in all of the patients. This mutation led to the change of p.Y755X in protein level and a truncated ROR2 protein losing integrant domains was generated. The mutation was detected in all the patients, but not in all the normal individuals of this family and 50 normal controls. This paper for the first time reported a c.2265C>A mutation in ROR2 gene of a family with BDB1 in China, which enriches ROR2 gene mutation spectrum in Chinese with BDB1.
LI Cong-Min, WANG Feng-Hu, SUN Wei-Wei, HAN Chu-Li, CHANG Meng-Xiu, FENG Hui-Gen
. Mutation analysis of the pathogenic gene in a Chinese family with Brachydactyly type B1[J]. Hereditas(Beijing), 2011
, 33(2)
: 147
-152
.
DOI: 10.3724/SP.J.1005.2011.00147
[1] Temtamy SA, Aglan MS. Brachydactyly. Orphanet J Rare Dis, 2008, 3: 15.
[2] Oldridge M, Temple IK, Santos HG, Gibbons RJ, Mustafa Z, Chapman KE, Loughlin J, Wilkie AOM. Brachydactyly type B: linkage to chromosome 9q22 and evidence for genetic heterogeneity. Am J Hum Genet, 1999, 64(2): 578-585.
[3] Schwabe GC, Tinschert S, Buschow C, Meinecke P, Wolff G, Gillessen-Kaesbach G, Oldridge M, Wilkie AOM, Kömec R, Mundlos S. Distinct mutations in the receptor tyrosine kinase gene ROR2 cause brachydactyly type B. Am J Hum Genet, 2000, 67(4): 822-831.
[4] http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs34431454.
[5] Oldridge M, Fortuna AM, Maringa M, Propping P, Man-sour S, Pollitt C, DeChiara TM, Kimble RB, Valenzuela DM, Yancopoulos GD, Wilkie AOM. Dominant mutations in ROR2, encoding an orphan receptor tyrosine kinase, cause brachydactyly type B. 2000, Nat Genet, 24(3): 275-278.
[6] http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs10992063.
[7] http://www.ncbi.nlm.nih.gov/SNP/snp_ref.cgi?rs=rs2230577.
[8] Hamamy H, Saleh N, Oldridge M, Al-Hadidy A, Ajlouni K. Brachydactyly type B1: report of a family with de novo ROR2 mutation. Clin Genet, 2006, 70(6): 538-540.
[9] Kjaer KW, Tiner M, Cingoz S, Karatosun V, Tommerup N, Mundlos S, Gunal I. A novel subtype of distal sympha-langism affecting only the 4th finger. Am J Med Genet Part A, 2009, 149A(7): 1571-1573.
[10] 杨威, 谭凤钦, 孙淼, 曾瑄, 刘杰, 刘国仰, 罗会元, 张学. 中国人遗传性B型短指(趾)家系中ROR2基因突变的鉴定. 中华医学遗传学杂志, 2004, 21(1): 61-63.
[11] Lv D, Luo Y, Yang W, Cao LH, Wen YR, Zhao XL, Sun M, Lo WH, Zhang X. A novel single-base deletion in ROR2 causes atypical brachydactyly type B1 with cutaneous syndactyly in a large Chinese family. J Hum Genet, 2009, 54(7): 422-425.
[12] Afzal AR, Jeffery S. One gene, two phenotypes: ROR2 mutations in autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B. Hum Mutat, 2003, 22(1): 1-11.
[13] Masiakowski P, Carroll RD. A novel family of cell surface receptors with tyrosine kinase-like domain. J Biol Chem.1992, 267(36): 26181-26190.
[14] Minami Y, Oishi I, Endo M, Nishita M. Ror-family receptor tyrosine kinases in noncanonical Wnt signaling: their implications in developmental morphogenesis and human diseases. Dev Dynam, 2010, 239(1): 1-15.
