Human malignant autosomal recessive osteopetrosis (ARO) is a genetically heterogeneous disorder caused by reduced bone resorption by osteoclasts. Mutations in the CLCN7 gene are responsible not only for a substantial portion of ARO patients, but also for other forms of osteopetrosis characterized by different severity and inheritance. The lack of a clear genotype/phenotype correlation makes genetic counselling a tricky issue for CLCN7-dependent osteopetrosis. Here we characterize the first homozygous interstitial deletion in 16p13.3, detected by array Comparative Genomic Hybridization (a-CGH) in an ARO patient of Jordanian origin. The deletion involved other genes beside CLCN7, while the proband displayed a classic ARO phenotype; however her early death did not allow more extensive clinical investigations. The identification of this novel genomic deletion involving a large part of the CLCN7 gene is of clinical relevance, especially in prenatal diagnosis, and suggests the possibility that this kind of mutation has been underestimated so far. This data highlights the need for alternative approaches to genetic analysis also in other ARO-causative genes.

A homozygous contiguous gene deletion in chromosome 16p13.3 leads to autosomal recessive osteopetrosis in a Jordanian patient

VALLI, ROBERTO;MASERATI, EMANUELA;
2012

Abstract

Human malignant autosomal recessive osteopetrosis (ARO) is a genetically heterogeneous disorder caused by reduced bone resorption by osteoclasts. Mutations in the CLCN7 gene are responsible not only for a substantial portion of ARO patients, but also for other forms of osteopetrosis characterized by different severity and inheritance. The lack of a clear genotype/phenotype correlation makes genetic counselling a tricky issue for CLCN7-dependent osteopetrosis. Here we characterize the first homozygous interstitial deletion in 16p13.3, detected by array Comparative Genomic Hybridization (a-CGH) in an ARO patient of Jordanian origin. The deletion involved other genes beside CLCN7, while the proband displayed a classic ARO phenotype; however her early death did not allow more extensive clinical investigations. The identification of this novel genomic deletion involving a large part of the CLCN7 gene is of clinical relevance, especially in prenatal diagnosis, and suggests the possibility that this kind of mutation has been underestimated so far. This data highlights the need for alternative approaches to genetic analysis also in other ARO-causative genes.
osteopetrosis, CLCN7, deletion, a-CGH, diagnosis
Pangrazio, A.; Frattini, A.; Valli, Roberto; Maserati, Emanuela; Susani, L.; Vezzoni, P.; Villa, A.; Al Herz, W.; Sobacchi, C.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/1760718
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