Recessive multiple epiphyseal dysplasia and Stargardt disease in two sisters. Issue 4 (16th March 2021)

• Record Type: Journal Article
• Authors: Gatticchi, Leonardo; Vešelényiová, Dominika; Miertus, Jan; Enrico Maltese, Paolo; Manara, Elena; Costantini, Alisia; Benedetti, Sabrina; Ďurovčíková, Darina; Krajcovic, Juraj; Bertelli, Matteo
• Is Part Of: Molecular genetics & genomic medicine. Volume 9:Issue 4(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-03-16
• Subjects: ABCA4 -- rMED -- SLC26A2 -- STGD1; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1630
• Languages: English
• ISSNs: 2324-9269

Abstract

ABSTRACT: Background: The rapid spread of genome‐wide next‐generation sequencing in the molecular diagnosis of rare genetic disorders has produced increasing evidence of multilocus genomic variations in cases with a previously well‐characterized molecular diagnosis. Here, we describe two patients with a rare combination of skeletal abnormalities and retinal dystrophy caused by variants in the SLC26A2 and ABCA4 genes, respectively, in a family with parental consanguinity. Methods: Next‐generation sequencing and Sanger sequencing were performed to obtain a molecular diagnosis for the retinal and skeletal phenotypes, respectively. Results: Genetic testing revealed that the sisters were homozygous for the p.(Cys653Ser) variant in SLC26A2 and heterozygous for the missense p.(Pro68Leu) and splice donor c.6386+2C>G variants in ABCA4 . Segregation analysis confirmed the carrier status of the parents. Conclusion: Despite low frequency of occurrence, the detection of multilocus genomic variations in a single disease gene‐oriented approach can provide accurate diagnosis even in cases with high phenotypic complexity. A targeted sequencing approach can detect relationships between observed phenotypes and underlying genotypes, useful for clinical management. Abstract : Sequencing techniques advancement enhances multilocus genomic variations detection. Here we described two rare cases of skeletal dysplasia with ophthalmic manifestations. Genetic testing revealed that the proband and her sister were affected by two rare diseases, the recessive multiple epiphyseal dysplasia and stargardt syndrome. We also provided a summary of drugs discovery for both the conditions.