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Fichera et al. J Transl Genet Genom 2020;4:114-32 Journal of Translational
DOI: 10.20517/jtgg.2020.16 Genetics and Genomics

Original Article Open Access

Assigning single clinical features to their
disease-locus in large deletions: the example of

chromosome 1q23-25 deletion syndrome

Marco Fichera , Lucia Saccuzzo , Sara Bertuzzo , Susan Marelli , Anna Cavallini , Romina Romaniello ,
4
5
3
1
1,2
5
Mirjana Kocova , Andrea Citterio , Isabella Fanizza , Antonio Trabacca , Angelica Pagliazzi , Silvia
3
6
7
8
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Guarducci , Sabrina Giglio , Orsetta Zuffardi , Maria Clara Bonaglia 3
10
8,9
9
1 Department of Biomedical and Biotechnological Sciences, Medical Genetics, University of Catania, Catania 95123, Italy.
2 Department of Laboratories, Oasi Research Institute-IRCCS, Troina 94018, Italy.
3 Cytogenetics Laboratory, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco 23842, Italy.
4 Medical Genetic Service,Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco 23842, Italy.
5 Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS Eugenio Medea, Bosisio Parini, Lecco 23842, Italy.
6 Department of Endocrinology and Genetics, University Clinic of Pediatrics, Medical Faculty, Ss. Cyril and Methodius University,
Skopje 1000, Republic of Macedonia.
7 Unit for Severe Disabilities in Developmental Age and Young Adults, Developmental Neurology and Neurorehabilitation,
Scientific Institute IRCCS E. Medea, Brindisi 72100, Italy.
8 Biomedical Experimental and Clinical Sciences “Mario Serio”, University of Florence, Florence 50121, Italy.
9 SOD Genetica Medica, Azienda Ospedaliero-Universitaria Meyer, Florence 50139, Italy.
10 Department of Molecular Medicine, University of Pavia, Pavia 27100, Italy.
Correspondence to: Dr. Maria Clara Bonaglia, Cytogenetics Laboratory, Scientific Institute, IRCCS Eugenio Medea, Via Don Luigi
Monza 20, Bosisio Parini, Lecco 23842, Italy. E-mail: clara.bonaglia@bp.lnf.it
How to cite this article: Fichera M, Saccuzzo L, Bertuzzo S, Marelli S, Cavallini A, Romaniello R, Kocova M, Citterio A, Fanizza I,
Trabacca A, Pagliazzi A, Guarducci S, Giglio S, Zuffardi O, Bonaglia MC. Assigning single clinical features to their disease-locus
in large deletions: the example of chromosome 1q23-25 deletion syndrome. J Transl Genet Genom 2020;4:114-32.
http://dx.doi.org/10.20517/jtgg.2020.16
Received: 17 Feb 2020 First Decision: 13 Apr 2020 Revised: 7 May 2020 Accepted: 28 May 2020 Available online: 18 Jun 2020
Science Editor: Tjitske Kleefstra Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Abstract
Aim: Assigning a disease-locus within the shortest regions of overlap (SRO) shared by deleted/duplicated
subjects presenting this disease is a robust mapping approach, although the presence of different malformation
traits and their attendance only in a part of the affected subjects can hinder the interpretation. To overcome the
problem of incomplete penetrance, we developed an algorithm that we applied to the deletion region 1q23.3-q25,
which contains three SROs, each contributing to the abnormal phenotype without clearly distinguishing between
the different malformations. We describe six new subjects, including a healthy father and his daughter, with
1q23.3-q25 deletion of different sizes. The aim of this study was to correlate specific abnormal traits to the
haploinsufficiency of specific gene/putative regulatory elements.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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