Sclerosteosis caused by a novel nonsense mutation of SOST in a consanguineous family.
Sclerosteosis, characterized by the hyperostosis of cranial and tubular bones, is a rare autosomal recessive hereditary disorder caused by mutation of SOST gene. Four nonsense mutations of SOST have been identified worldwide. Here, we report two affected siblings who carried a novel nonsense mutation of SOST in a consanguineous family from China. The proband manifested typical symptoms of sclerosteosis, whereas the symptoms were absent in another affected sibling. Two nucleotide substitutions in exon 2 of SOST were identified, c.444_445TC>AA, resulting in a premature stop codon, p.Cys148→Stop. This truncated mutation loses 66 amino acid residues which contain 3 cysteine residues of the cysteine-knot motif, leading to loss of function of SOST. The symptoms of sclerosteosis may be clinically heterogeneous in some patients, even with the same mutation. Our results support the notion that founder effects from the ancestors contribute to the disease onset.
Department of Endocrinology and Metabolism, Wuhan, P. R. China.
Wen-Tao
WT
He
Department of Cardiology, Wuhan, P. R. China.
Chen
C
Chen
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P. R. China.
Chu
C
Pan
Department of Endocrinology and Metabolism, Wuhan, P. R. China.
Mu-Xun
MX
Zhang
Department of Endocrinology and Metabolism, Wuhan, P. R. China.
Xue-Feng
XF
Yu
Department of Cardiology, Wuhan, P. R. China.
Dao-Wen
DW
Wang
Department of Endocrinology and Metabolism, Wuhan, P. R. China.
Shu-Hong
SH
Hu
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics*; D003241:Consanguinity; D005190:Family; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015576:Hyperostosis / Q000000981:diagnostic imaging / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011859:Radiography; D013576:Syndactyly / Q000000981:diagnostic imaging / Q000235:genetics*; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D018389:Codon, Nonsense; D005819:Genetic Markers; C422903:SOST protein, human
SOST; consanguineous family; nonsense mutation; sclerostin