A Known SOST Gene Mutation Causes Sclerosteosis in a Familial and an Isolated Case from Brazilian Origin

Abstract

Sclerosteosis is a severe, rare, autosomal recessive bone condition that is characterized by a progressive craniotubular hyperostosis. The main features are a significant sclerosis of the long bones, ribs, pelvis, and skull, leading to facial distortion and entrapment of cranial nerves. Clinical features include a tall stature, nail dysplasia, cutaneous syndactyly of some fingers, and raised intracranial pressure. The sclerosteosis gene has been mapped to chromosome 17q12-21 and is currently known as the SOST gene encoding the sclerostin protein. Here, we report on one familial and one isolated case of Brazilian origin with the clinical and molecular diagnosis of sclerosteosis. The radiological and clinical features are described, and the diagnosis of sclerosteosis was confirmed in both cases by mutation analysis of the SOST gene showing a homozygous nonsense mutation (Trp124X) in the two patients. We reported this mutation previously in other sclerosteosis patients from a consanguineous Brazilian family. Interestingly, all three families were from the same state in Brazil, but they denied familial relationship. These patients confirm the clinical picture as found in other cases with a loss of function mutation in the SOST gene.

Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia

“…Thus, there is a clear distinction between CDD and sclerosteosis. Sclerosteosis is an autosomal recessive disorder resulted from a null mutation of SOST, and a heterozygote carrier of the SOST null mutation is asymptomatic except for incidental reports of mildly increased bone mineral density (Balemans et al 2001;Brunkow et al 2001;Kim et al 2008;Uitterlinden et al 2004). Although several cases of CDD have been reported in the literature, the genetic mode of transmission remained inconclusive.…”

A Review of Osteocyte Function and the Emerging Importance of Sclerostin

“…In sclerosteosis, patients have increased bone mineral density and syndactyly due to sclerostin loss-of-function mutations. Only six mutations have been identified in sclerosteosis, and they involve both the sclerostin gene and LRP5 26,27,[102][103][104] . van Buchem disease is a similar, less severe disease of generalized osteosclerosis.…”

Sclerostin: Current Knowledge and Future Perspectives

“…Five mutations have so far been identified in patients with sclerosteosis, of which three introduce a premature termination codon and the others interfere with splicing of the gene [16–19]. No mutations within this gene could be found in patients with van Buchem disease, but instead a 52-kb deletion 35 kb downstream of the SOST gene was identified [20, 21].…”