Two-hundred and thirty-four Italian patients with a clinical diagnosis of macular, cone and cone-rod dystrophies (MD, CD, and CRD) were examined using next-generation sequencing (NGS) and gene sequencing panels targeting a specific set of genes, Sanger sequencing and—when necessary—multiplex ligation-dependent probe amplification (MLPA) to diagnose the molecular cause of the aforementioned diseases. When possible, segregation analysis was performed in order to confirm unsolved cases. Each patient’s retinal phenotypic characteristics were determined using focal and full-field ERGs, perimetry, spectral domain optical coherence tomography and fundus autofluorescence. We identified 236 potentially causative variants in 136 patients representing the 58.1% of the total cohort, 43 of which were unpublished. After stratifying the patients according to their clinical suspicion, the diagnostic yield was 62.5% and 53.8% for patients with MD and for those with CD/CRD, respectively. The mode of inheritance of all cases confirmed by genetic analysis was 70% autosomal recessive, 26% dominant, and 4% X-linked. The main cause (59%) of both MD and CD/CRD cases was the presence of variants in the ABCA4 gene, followed by variants in PRPH2 (9%) and BEST1 (6%). A careful morpho-functional evaluation of the phenotype, together with genetic counselling, resulted in an acceptable diagnostic yield in a large cohort of Italian patients. Our study emphasizes the role of targeted NGS to diagnose MDs, CDs, and CRDs, as well as the clinical usefulness of segregation analysis for patients with unsolved diagnosis.

Falsini, B., Placidi, G., De Siena, E., Chiurazzi, P., Minnella, A. M., Savastano, M. C., Ziccardi, L., Parisi, V., Iarossi, G., Percio, M., Pitekova, B., Marceddu, G., Maltese, P. E., Bertelli, M., Genetic characteristics of 234 Italian patients with macular and cone/cone-rod dystrophy, <<SCIENTIFIC REPORTS>>, 2022; 12 (1): 3774-N/A. [doi:10.1038/s41598-022-07618-1] [http://hdl.handle.net/10807/200883]

Genetic characteristics of 234 Italian patients with macular and cone/cone-rod dystrophy

Falsini, Benedetto;Placidi, Giorgio;Chiurazzi, Pietro;Minnella, Angelo Maria;Savastano, Maria Cristina;Maltese, Paolo Enrico;
2022

Abstract

Two-hundred and thirty-four Italian patients with a clinical diagnosis of macular, cone and cone-rod dystrophies (MD, CD, and CRD) were examined using next-generation sequencing (NGS) and gene sequencing panels targeting a specific set of genes, Sanger sequencing and—when necessary—multiplex ligation-dependent probe amplification (MLPA) to diagnose the molecular cause of the aforementioned diseases. When possible, segregation analysis was performed in order to confirm unsolved cases. Each patient’s retinal phenotypic characteristics were determined using focal and full-field ERGs, perimetry, spectral domain optical coherence tomography and fundus autofluorescence. We identified 236 potentially causative variants in 136 patients representing the 58.1% of the total cohort, 43 of which were unpublished. After stratifying the patients according to their clinical suspicion, the diagnostic yield was 62.5% and 53.8% for patients with MD and for those with CD/CRD, respectively. The mode of inheritance of all cases confirmed by genetic analysis was 70% autosomal recessive, 26% dominant, and 4% X-linked. The main cause (59%) of both MD and CD/CRD cases was the presence of variants in the ABCA4 gene, followed by variants in PRPH2 (9%) and BEST1 (6%). A careful morpho-functional evaluation of the phenotype, together with genetic counselling, resulted in an acceptable diagnostic yield in a large cohort of Italian patients. Our study emphasizes the role of targeted NGS to diagnose MDs, CDs, and CRDs, as well as the clinical usefulness of segregation analysis for patients with unsolved diagnosis.
2022
Inglese
Falsini, B., Placidi, G., De Siena, E., Chiurazzi, P., Minnella, A. M., Savastano, M. C., Ziccardi, L., Parisi, V., Iarossi, G., Percio, M., Pitekova, B., Marceddu, G., Maltese, P. E., Bertelli, M., Genetic characteristics of 234 Italian patients with macular and cone/cone-rod dystrophy, <<SCIENTIFIC REPORTS>>, 2022; 12 (1): 3774-N/A. [doi:10.1038/s41598-022-07618-1] [http://hdl.handle.net/10807/200883]
File in questo prodotto:
File Dimensione Formato  
41598_2022_Article_7618.pdf

accesso aperto

Descrizione: Genetic characteristics of 234 Italian patients with macular and cone/cone‐rod dystrophy
Tipologia file ?: Versione Editoriale (PDF)
Licenza: Creative commons
Dimensione 1.92 MB
Formato Adobe PDF
1.92 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/200883
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 5
social impact