Open AccessRecessive multiple epiphyseal dysplasia and Stargardt disease in two sisters
Author(s) -
Gatticchi Leonardo,
Vešelényiová Dominika,
Miertus Jan,
Enrico Maltese Paolo,
Manara Elena,
Costantini Alisia,
Benedetti Sabrina,
Ďurovčíková Darina,
Krajcovic Juraj,
Bertelli Matteo
Publication year - 2021
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1630
Subject(s) - sanger sequencing , abca4 , stargardt disease , missense mutation , genetics , biology , consanguinity , phenotype , exome sequencing , dna sequencing , gene , bioinformatics
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.