A novel single-base deletion in ROR2 causes atypical brachydactyly type B1 with cutaneous syndactyly in a large Chinese family.
Mutations in ROR2, encoding the receptor tyrosine kinase-like orphan receptor 2, cause two distinct skeletal diseases: autosomal dominant brachydactyly type B1 (BDB1) and autosomal recessive Robinow syndrome. In a large Chinese family with a limb phenotype, consisting of atypical BDB1 and cutaneous syndactyly of varying degrees, we performed a two-point linkage analysis using microsatellite markers on 2q33-q37 and 9q22.31, and found a significant linkage to the ROR2 locus. We identified a novel single-base deletion in ROR2, c.2243delC (p.W749fsX24), and confirmed its segregation with the limb phenotype in the family. This deletion is predicted to produce a truncated ROR2 protein with an additional C-terminal polypeptide of 24 amino-acid residues. To the best of our knowledge, the deletion represents the second ROR2 mutation associated with a BDB1-syndactyly phenotype.
Lv
Dan
D
McKusick-Zhang Center for Genetic Medicine and State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Luo
Yang
Y
Yang
Wei
W
Cao
Lihua
L
Wen
Yaran
Y
Zhao
Xiuli
X
Sun
Miao
M
Lo
Wilson H-Y
WH
Zhang
Xue
X
D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D012868:Skin Abnormalities / Q000150:complications* / Q000235:genetics*; D013576:Syndactyly / Q000150:complications* / Q000235:genetics*
C078717:ROR2 protein, human; D057050:Receptor Tyrosine Kinase-like Orphan Receptors