Small supernumerary marker chromosome 15 and a ring chromosome 15 associated with a 15q26.3 deletion excluding the IGF1R gene

Abstract

Array comparative genomic hybridization is essential in the investigation of chromosomal rearrangements associated with epilepsy, intellectual disability, and dysmorphic features. In many cases deletions, duplications, additional marker chromosomes, and ring chromosomes originating from chromosome 15 lead to abnormal phenotypes. We present a child with epilepsy, cardiac symptoms, severely delayed mental and growth development, behavioral disturbances and characteristic dysmorphic features showing a ring chromosome 15 and a small supernumerary marker chromosome. Array CGH detected a 1 Mb deletion of 15q26.3 in a ring chromosome 15 and a 2.6 Mb copy number gain of 15q11.2 corresponding to a small supernumerary marker chromosome involving proximal 15q. Our findings add to previously published results of 15q11q13 duplications and 15q26 terminal deletions. Based on our study we can support the previous reported limited information about the role of SELS, SNRPA1, and PCSK6 genes in the development of the heart morphology. On the other hand, we found that the copy number loss of our patient did not involve the IGF1R gene which is often associated with growth retardation (short stature and decreased weight). We hypothesize that haploinsufficiency of the 15q26 genomic region distal to IGF1R gene might be related to growth disturbance; however, presence of the ring chromosome 15 itself could also be responsible for the growth delay.

Ring chromosome 15 – cytogenetics and mapping arrays: a case report and review of the literature

“…We identified that there is a common breakpoint in most: the genomic region 15q26. Duplication, deletions, and gains in this region could be associated with different phenotypic manifestations as the region harbors different genes [ 15 ]. For instance, insulin-like growth factor 1 receptor ( IGF1R ) is involved in normal growth and development [ 16 ].…”

Partial 5p Gain and 15q Loss in Three Patients from a Family with a t(5;15)(p13.3;q26.3) Translocation

“…Deletions of the 15q26.2qter region, for instance, have been described in a few patients with intrauterine and postnatal growth retardation, congenital heart defects, intellectual disability, triangular facial shape, skeletal anomalies such as clinodactyly and brachydactyly, and other minor abnormalities related to the shape of the nasal bridge and the eyes [Rump et al, 2008;Ester et al, 2009;Rudaks et al, 2011;Poot et al, 2013;O'Riordan et al, 2017;Szabó et al, 2018;Santos et al, 2020]. Haploinsufficiency of the IGF1R gene has been postulated as the main cause of most of these clinical features since they are similar to the ones caused by single mutations in this gene [Walenkamp et al, 2008] as well as its partial deletion [Veenma et al, 2010], especially in regard to growth deficiency.…”

“…We could not properly evaluate this patient, but his blood samples were collected for karyotype. Pinson et al, 2005;Rujirabanjerd et al, 2007;Rump et al, 2008;Walenkamp et al, 2008;Ester et al, 2009;Bruce et al, 2010;Lin et al, 2010;Dateki et al, 2011;Rudaks et al, 2011;Poot et al, 2013;O'Riordan et al, 2017;Santos et al, 2020. b Lucaccioni et al, 2015;Szabó et al, 2018;DECIPHER: 270050, 265742, 401263, 251400, 353687, 331451, 331238, 286496, 280979. c Chia et al, 1987;Webb et al, 1988;Rethoré et al, 1989;Zenger-Hain et al, 1993;Chen et al, 1995;Baialardo et al, 2003;Cervera et al, 2005. Bellucco/Favilla/Perrone/Melaragno Cytogenet Genome Res 2020;160:589-596 592 DOI: 10.1159/000511235…”

“…Terminal deletions of the long arm of chromosome 15, on the other hand, are responsible for a variety of clinical features and multiple congenital abnormalities [Tümer et al, 2004;Li et al, 2008], being associated with growth deficiency, intellectual disability, breathing problems at birth, feeding difficulties, abnormal facial features, and anomalies of the hands and feet [Poot et al, 2013;Szabó et al, 2018]. Chromosome 15q26 deletion syndrome (OMIM #612626) has been described in a few patients with such clinical features.…”

“…Chromosome 15q26 deletion syndrome (OMIM #612626) has been described in a few patients with such clinical features. Although its molecular basis relies on a 5.8-Mb deletion of this region, encompassing the insulin-like growth factor 1 receptor (IGF1R) gene (OMIM *147370), smaller deletions that do not include this gene have also been described and associated with variable phenotypes of the syndrome [Poot et al, 2013;Szabó et al, 2018]. There is great clinical variability among the patients with 15q26 deletions, even when they present deletions of the same size.…”