Recessive Multiple Epiphyseal Dysplasia and Stargardt Disease in Two Sisters

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2021 Mar 16

PMID 33724725

Citations 3

Authors

Leonardo Gatticchi

Dominika Veselenyiova

Jan Miertus

Paolo Enrico Maltese

Elena Manara

Alisia Costantini

Sabrina Benedetti

Darina durovcikova

Juraj Krajcovic

Matteo Bertelli

Affiliations

Soon will be listed here.

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.

Citing Articles

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