Purpose: To describe the clinical and molecular findings of an Italian family with a new mutation in the choroideremia (CHM) gene. Methods: We performed a comprehensive ophthalmologic examination, fundus photography, macular optical coherence tomography, perimetry, electroretinography, and fluorescein angiography in an Italian family. The clinical diagnosis was supported by western blot analysis of lymphoblastoid cell lines from patients with CHM and carriers, using a monoclonal antibody against the 415 C-terminal amino acids of Rab escort protein-1 (REP-1). Sequencing of the CHM gene was undertaken on genomic DNA from affected men and carriers; the RNA transcript was analyzed with reverse transcriptase-PCR. Results: The affected men showed a variability in the rate of visual change and in the degree of clinical and functional ophthalmologic involvement, mainly age-related, while the women displayed aspecific areas of chorioretinal degeneration. Western blot did not show a detectable amount of normal REP-1 protein in affected men who were hemizygous for a novel mutation, c.819+2T>A at the donor splicing site of intron 6 of the CHM gene; the mutation was confirmed in heterozygosity in the carriers. Conclusions: Western blot of the REP-1 protein confirmed the clinical diagnosis, and molecular analysis showed the new in-frame mutation, c.819+2T>A, leading to loss of function of the REP-1 protein. These results emphasize the value of a diagnostic approach that correlates genetic and ophthalmologic data for identifying carriers in families with CHM. An early diagnosis might be crucial for genetic counseling of this type of progressive and still untreatable disease.

Clinical and genetic studies in a family with a new splice-site mutation in the choroideremia gene / Contestabile, Maria Teresa; Piane, Maria; Pasquale N., Cascone Nc; N. C., Cascone; N., Pasquale; Ciarnella, Angela; Recupero, Santi Maria; Chessa, Luciana. - In: MOLECULAR VISION. - ISSN 1090-0535. - 20:(2014), pp. 325-333.

Clinical and genetic studies in a family with a new splice-site mutation in the choroideremia gene

CONTESTABILE, Maria Teresa;PIANE, Maria;CIARNELLA, Angela;RECUPERO, Santi Maria;CHESSA, Luciana
2014

Abstract

Purpose: To describe the clinical and molecular findings of an Italian family with a new mutation in the choroideremia (CHM) gene. Methods: We performed a comprehensive ophthalmologic examination, fundus photography, macular optical coherence tomography, perimetry, electroretinography, and fluorescein angiography in an Italian family. The clinical diagnosis was supported by western blot analysis of lymphoblastoid cell lines from patients with CHM and carriers, using a monoclonal antibody against the 415 C-terminal amino acids of Rab escort protein-1 (REP-1). Sequencing of the CHM gene was undertaken on genomic DNA from affected men and carriers; the RNA transcript was analyzed with reverse transcriptase-PCR. Results: The affected men showed a variability in the rate of visual change and in the degree of clinical and functional ophthalmologic involvement, mainly age-related, while the women displayed aspecific areas of chorioretinal degeneration. Western blot did not show a detectable amount of normal REP-1 protein in affected men who were hemizygous for a novel mutation, c.819+2T>A at the donor splicing site of intron 6 of the CHM gene; the mutation was confirmed in heterozygosity in the carriers. Conclusions: Western blot of the REP-1 protein confirmed the clinical diagnosis, and molecular analysis showed the new in-frame mutation, c.819+2T>A, leading to loss of function of the REP-1 protein. These results emphasize the value of a diagnostic approach that correlates genetic and ophthalmologic data for identifying carriers in families with CHM. An early diagnosis might be crucial for genetic counseling of this type of progressive and still untreatable disease.
2014
01 Pubblicazione su rivista::01a Articolo in rivista
Clinical and genetic studies in a family with a new splice-site mutation in the choroideremia gene / Contestabile, Maria Teresa; Piane, Maria; Pasquale N., Cascone Nc; N. C., Cascone; N., Pasquale; Ciarnella, Angela; Recupero, Santi Maria; Chessa, Luciana. - In: MOLECULAR VISION. - ISSN 1090-0535. - 20:(2014), pp. 325-333.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/558603
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