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15q24.1 BP4-BP1 microdeletion unmasking paternally inherited functional polymorphisms combined with distal 15q24.2q24.3 duplication in a patient with epilepsy, psychomotor delay, overweight, ventricular arrhythmia.

Authors :
Huynh, Minh-Tuan
Lambert, Anne-Sophie
Tosca, Lucie
Petit, François
Philippe, Christophe
Parisot, Frédéric
Benoît, Virginie
Linglart, Agnès
Brisset, Sophie
Tran, Cong Toai
Tachdjian, Gérard
Receveur, Aline
Source :
European Journal of Medical Genetics. Aug2018, Vol. 61 Issue 8, p459-464. 6p.
Publication Year :
2018

Abstract

15q24 microdeletion and microduplication syndromes are genetic disorders caused by non-allelic homologous recombination between low-copy repeats (LCRs) in the 15q24 chromosome region. Individuals with 15q24 microdeletion and microduplication syndromes share a common 1.2 Mb critical interval, spanning from LCR15q24B to LCR15q24C. Patients with 15q24 microdeletion syndrome exhibit distinct dysmorphic features, microcephaly, variable developmental delay, multiples congenital anomalies while individuals with reciprocal 15q24 microduplication syndrome show mild developmental delay, facial dysmorphism associated with skeletal and genital abnormalities. We report the first case of a 10 year-old girl presenting mild developmental delay, psychomotor retardation, epilepsy, ventricular arrhythmia, overweight and idiopathic central precocious puberty. 180K array-CGH analysis identified a 1.38 Mb heterozygous interstitial 15q24.1 BP4-BP1 microdeletion including HCN4 combined with a concomitant 2.6 Mb heterozygous distal 15q24.2q24.3 microduplication. FISH analysis showed that both deletion and duplication occurred de novo in the proband. Of note, both copy number imbalances did not involve the 1.2 Mb minimal deletion/duplication critical interval of the 15q24.1q24.2 chromosome region (74.3–75.5 Mb). Sequencing of candidate genes for epilepsy and obesity showed that the proband was hemizygous for paternal A-at risk allele of BBS4 rs7178130 and NPTN rs7171755 predisposing to obesity, epilepsy and intellectual deficits. Our study highlights the complex interaction of functional polymorphisms and/or genetic variants leading to variable clinical manifestations in patients with submicroscopic chromosomal aberrations. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
17697212
Volume :
61
Issue :
8
Database :
Academic Search Index
Journal :
European Journal of Medical Genetics
Publication Type :
Academic Journal
Accession number :
130419065
Full Text :
https://doi.org/10.1016/j.ejmg.2018.03.005