Sclerosing bone dysplasias with hallmarks of dysosteosclerosis in four patients carrying mutations in SLC29A3 and TCIRG1
2019
Abstract The osteopetroses and related sclerosing bone dysplasias can have a broad range of manifestations. Especially in the milder forms, sandwich vertebrae are an easily recognizable and reliable radiological hallmark. We report on four patients from three families presenting with sandwich vertebrae and platyspondyly. The long bone phenotypes were discordant with one patient showing modeling defects and patchy
osteosclerosis, while the second displayed only metaphyseal sclerotic bands, and the third and fourth had extreme metaphyseal flaring with uniform
osteosclerosis. Two of the four patients had experienced
pathological fractures, two had developmental delay, but none showed cranial nerve damage,
hepatosplenomegaly, or
bone marrow failure. According to these clinical features the diagnoses ranged between intermediate autosomal recessive
osteopetrosisand dysosteosclerosis. After exclusion of mutations in
CLCN7we performed gene panel and
exome sequencing. Two novel mutations in SLC29A3 were found in the first two patients. In the third family a
TCIRG1C-terminal
frameshift mutationin combination with a mutation at position +4 in intron 2 were detected. Our study adds two cases to the small group of individuals with SLC29A3 mutations diagnosed with dysosteosclerosis, and expands the phenotypic variability. The finding that intermediate autosomal recessive
osteopetrosisdue to
TCIRG1
splice site mutationscan also present with platyspondyly further increases the molecular heterogeneity of dysosteosclerosis-like sclerosing bone dysplasias.
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