title: 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.
authors.forename: Chong Ae
authors.initials: CA
authors.lastname: Kim
authors.forename: Rachel
authors.initials: R
authors.lastname: Honjo
authors.forename: Débora
authors.initials: D
authors.lastname: Bertola
authors.forename: Lílian
authors.initials: L
authors.lastname: Albano
authors.forename: Luiz
authors.initials: L
authors.lastname: Oliveira
authors.forename: Sumatra
authors.initials: S
authors.lastname: Jales
authors.forename: José
authors.initials: J
authors.lastname: Siqueira
authors.forename: Arthur
authors.initials: A
authors.lastname: Castilho
authors.forename: Wendy
authors.initials: W
authors.lastname: Balemans
authors.forename: Elke
authors.initials: E
authors.lastname: Piters
authors.forename: Karen
authors.initials: K
authors.lastname: Jennes
authors.forename: Wim
authors.initials: W
authors.lastname: Van Hul
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D001938:Brazil; D002648:Child; D018389:Codon, Nonsense; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015576:Hyperostosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D008297:Male; D010026:Osteosclerosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D011859:Radiography; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D018389:Codon, Nonsense; D005819:Genetic Markers; C422903:SOST protein, human