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

Abstract

Several patients with 5p duplication or 15q deletion have been reported in the literature, involving different chromosome regions and clinical features. Here, we describe a family in which we identified a 30-Mb 5p15.33p13.3 gain and a 2.5-Mb 15q26.3 loss in 3 individuals, due to a balanced familial translocation between chromosomes 5p and 15q. They presented a similar combination of clinical findings related to their genetic imbalances, but there were also phenotypic differences between them. Our analyses show that their clinical picture is mostly caused by the loss in 15q and not the gain in 5p, despite its much larger size. Our findings suggest that other genes, besides the <i>IGF1R</i> gene, in the 15q26.3 region, such as the <i>CHSY1</i> gene, may have a great impact on the clinical picture of the syndrome. Our data emphasize the importance of detailed cytogenomic and clinical analyses for an accurate diagnosis, prognosis, and genetic counseling, providing an opportunity to improve genotype-phenotype correlations of patients with partial 5p duplication and 15q deletion syndromes.

Spread of X‐chromosome inactivation into autosomal regions in patients with unbalanced X‐autosome translocations and its phenotypic effects

“…For all the patients, a statistically significant increase in fluorescence is observed in the autosomal portions of the derivative chromosomes, compared to the internal (normal chromosome) and external controls ( † ) *p ≤ .05, **p ≤ .01 and p ≤ .005 [Color figure can be viewed at wileyonlinelibrary.com] Clayton-Smith & Laan, 2003), suggesting that the spread of XCI may have occurred in this region, but have also been incomplete. Moreover, deletions of the 15qter region have also been associated with different phenotypical characteristics that our patient presents, such as cerebral malformations, neurodevelopmental delay, speech disorders, epileptic syndrome, facial dysmorphisms and café-au-lait spots (Bellucco et al, 2020;O'Riordan et al, 2016;Poot et al, 2013;Roback et al, 1991;Rump et al, 2008;Tönnies et al, 2001;Veenma et al, 2010).…”

“…Even though our patient presented some phenotypic characteristics that can be associated with the syndrome, such as gait disorders, speech impairment and facial dysmorphisms, his clinical picture lacks some key‐features, such as skin and hair hypopigmentation and specific behavioral characteristics (Clayton‐Smith & Laan, 2003), suggesting that the spread of XCI may have occurred in this region, but have also been incomplete. Moreover, deletions of the 15qter region have also been associated with different phenotypical characteristics that our patient presents, such as cerebral malformations, neurodevelopmental delay, speech disorders, epileptic syndrome, facial dysmorphisms and café‐au‐lait spots (Bellucco et al, 2020; O'Riordan et al, 2016; Poot et al, 2013; Roback et al, 1991; Rump et al, 2008; Tönnies et al, 2001; Veenma et al, 2010).…”

15q26.3 deletions distal to IGF1R cause growth retardation, congenital heart defect and skeletal anomalies: Case report and review of literature

“…Several cases with 15q26 deletions distal to IGF1R and NR2F2 have been reported with intrauterine and postnatal growth restriction, intellectual disability, dysmorphic facial features, congenital heart defects, and eye and skeletal anomalies (Table S1). In these patients, 15q26.3 deletions occurred as a result of chromosomal rearrangements such as ring chromosomes (Szabo et al, 2018; Tewari et al, 2017), unbalanced translocation involving 15q26.3 (Bellucco et al, 2021; Choucair et al, 2015), or pure deletions (van Duyvenvoorde et al, 2014).…”

“…Deletions of 15q26 are rare chromosomal rearrangements that are associated with variable degree of intrauterine and/or postnatal growth retardation, intellectual disability, microcephaly, congenital anomalies such as heart defects, skeletal, and eye anomalies (Benbouchta et al, 2021; Poot et al, 2013). Deletions at 15q26 may occur as a de novo event leading to a pure deletion or as a consequence of ring chromosome 15 formation or may be due to the presence of an unbalanced translocation that includes the loss of 15q26 (Bellucco et al, 2021; Szabo et al, 2018; van Duyvenvoorde et al, 2014). Over 60 patients with deletions involving 15q26 have been documented in the literature and in the DECIPHER database (https://www.deciphergenomics.org/) and the majority of these deletions include 15q26.2‐>q26.3 (Benbouchta et al, 2021; Poot et al, 2013; Szabo et al, 2018; van Duyvenvoorde et al, 2014).…”

“…In this report, we present a female child with intrauterine and postnatal growth restriction, congenital heart defect and skeletal anomalies.CMA revealed a possible de novo deletion of approximately 2.1 Mb at 15q26.3. Deletions of 15q26 region have been rarely described in the literature in patients with intrauterine and/or postnatal growth retardation, intellectual disability, congenital heart defects, skeletal anomalies, eye anomalies, and dysmorphic facial features(Bellucco et al, 2021;Benbouchta et al, 2021;Choucair et al, 2015;Fan et al, 2018;Lindstrand et al, 2019;Roberts et al, 2014;Sansovic et al, 2017;Szabo et al, 2018;Tewari et al, 2017;van Duyvenvoorde et al, 2014;Xu et al, 2014;Yu et al, 2011). Haploinsufficiency of IGF1R is thought to be contributing to growth restriction, intellectual disability, facial dysmorphism, and skeletal anomalies(Walenkamp et al, 2019), whereas loss of function variants in NR2F2 have been postulated to be contributing to the congenital heart defect(Matsunami et al, 2018;Upadia et al, 2018).…”