Recessive multiple epiphyseal dysplasia and Stargardt disease in two sisters
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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2021-04-01
|
Series: | Molecular Genetics & Genomic Medicine |
Subjects: | |
Online Access: | https://doi.org/10.1002/mgg3.1630 |
id |
doaj-25fb7753fd374e0cb98cade89e2bc9c6 |
---|---|
record_format |
Article |
spelling |
doaj-25fb7753fd374e0cb98cade89e2bc9c62021-05-15T17:47:34ZengWileyMolecular Genetics & Genomic Medicine2324-92692021-04-0194n/an/a10.1002/mgg3.1630Recessive multiple epiphyseal dysplasia and Stargardt disease in two sistersLeonardo Gatticchi0Dominika Vešelényiová1Jan Miertus2Paolo Enrico Maltese3Elena Manara4Alisia Costantini5Sabrina Benedetti6Darina Ďurovčíková7Juraj Krajcovic8Matteo Bertelli9Department of Experimental Medicine Laboratory of Biochemistry University of Perugia Perugia ItalyDepartment of Biology Faculty of Natural Sciences University of Ss. Cyril and Methodius Trnava SlovakiaGénius n.o Trnava SlovakiaMAGI’s Lab, Genetic Testing Laboratory Rovereto ItalyMAGI Euregio Bolzano ItalyMAGI’s Lab, Genetic Testing Laboratory Rovereto ItalyMAGI’s Lab, Genetic Testing Laboratory Rovereto ItalyInstitute of Genetics and Molecular Medicine Faculty of Medicine Slovak Healthcare University Bratislava SlovakiaDepartment of Biology Faculty of Natural Sciences University of Ss. Cyril and Methodius Trnava SlovakiaMAGI’s Lab, Genetic Testing Laboratory Rovereto ItalyABSTRACT 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.https://doi.org/10.1002/mgg3.1630ABCA4rMEDSLC26A2STGD1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Leonardo Gatticchi Dominika Vešelényiová Jan Miertus Paolo Enrico Maltese Elena Manara Alisia Costantini Sabrina Benedetti Darina Ďurovčíková Juraj Krajcovic Matteo Bertelli |
spellingShingle |
Leonardo Gatticchi Dominika Vešelényiová Jan Miertus Paolo Enrico Maltese Elena Manara Alisia Costantini Sabrina Benedetti Darina Ďurovčíková Juraj Krajcovic Matteo Bertelli Recessive multiple epiphyseal dysplasia and Stargardt disease in two sisters Molecular Genetics & Genomic Medicine ABCA4 rMED SLC26A2 STGD1 |
author_facet |
Leonardo Gatticchi Dominika Vešelényiová Jan Miertus Paolo Enrico Maltese Elena Manara Alisia Costantini Sabrina Benedetti Darina Ďurovčíková Juraj Krajcovic Matteo Bertelli |
author_sort |
Leonardo Gatticchi |
title |
Recessive multiple epiphyseal dysplasia and Stargardt disease in two sisters |
title_short |
Recessive multiple epiphyseal dysplasia and Stargardt disease in two sisters |
title_full |
Recessive multiple epiphyseal dysplasia and Stargardt disease in two sisters |
title_fullStr |
Recessive multiple epiphyseal dysplasia and Stargardt disease in two sisters |
title_full_unstemmed |
Recessive multiple epiphyseal dysplasia and Stargardt disease in two sisters |
title_sort |
recessive multiple epiphyseal dysplasia and stargardt disease in two sisters |
publisher |
Wiley |
series |
Molecular Genetics & Genomic Medicine |
issn |
2324-9269 |
publishDate |
2021-04-01 |
description |
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. |
topic |
ABCA4 rMED SLC26A2 STGD1 |
url |
https://doi.org/10.1002/mgg3.1630 |
work_keys_str_mv |
AT leonardogatticchi recessivemultipleepiphysealdysplasiaandstargardtdiseaseintwosisters AT dominikaveselenyiova recessivemultipleepiphysealdysplasiaandstargardtdiseaseintwosisters AT janmiertus recessivemultipleepiphysealdysplasiaandstargardtdiseaseintwosisters AT paoloenricomaltese recessivemultipleepiphysealdysplasiaandstargardtdiseaseintwosisters AT elenamanara recessivemultipleepiphysealdysplasiaandstargardtdiseaseintwosisters AT alisiacostantini recessivemultipleepiphysealdysplasiaandstargardtdiseaseintwosisters AT sabrinabenedetti recessivemultipleepiphysealdysplasiaandstargardtdiseaseintwosisters AT darinadurovcikova recessivemultipleepiphysealdysplasiaandstargardtdiseaseintwosisters AT jurajkrajcovic recessivemultipleepiphysealdysplasiaandstargardtdiseaseintwosisters AT matteobertelli recessivemultipleepiphysealdysplasiaandstargardtdiseaseintwosisters |
_version_ |
1721440560707796992 |