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Case Reports
. 2018 Feb 5:11:15.
doi: 10.1186/s13039-018-0365-5. eCollection 2018.

Rare partial octosomy and hexasomy of 15q11-q13 associated with intellectual impairment and development delay: report of two cases and review of literature

Haiyu Li  1 , Juan Du  1   2 , Wen Li  1   2 , Dehua Cheng  1   2 , Wenbin He  1   2 , Duo Yi  2 , Bo Xiong  2 , Shimin Yuan  2 , Chaofeng Tu  1 , Lanlan Meng  2 , Aixiang Luo  1 , Ge Lin  1   2 , Guangxiu Lu  1   2 , Yue-Qiu Tan  1   2
Affiliations
Case Reports

Rare partial octosomy and hexasomy of 15q11-q13 associated with intellectual impairment and development delay: report of two cases and review of literature

Haiyu Li et al. Mol Cytogenet. .

Abstract

Background: Small supernumerary marker chromosomes (sSMCs) are common structurally abnormal chromosomes that occur in 0.288% of cases of mental retardation. Isodicentric 15 (idic(15)) is common in sSMCs and usually leads to a rare chromosome disorder with distinctive clinical phenotypes, including early central hypotonia, developmental delay, epilepsy, and autistic behavior. It was previously shown that the partial tetrasomy 15q and partial hexasomy 15q syndromes are usually caused by one and two extra idic(15), respectively. Karyotypes containing a mosaic partial octosomy 15q resulting from three extra idic(15) have rarely been reported.

Case presentation: Two patients with profound intellectual impairment, development delay and hyperpigmentation were recruited for this study. The phenotype was relatively more severe in patient 1 than in patient 2. Conventional cytogenetic analysis of peripheral blood obtained from patients 1 and 2 revealed rare mosaic karyotypes containing sSMCs, i.e., mos 49,XX,+mar × 3[83]/48,XX,+mar × 2[7]/46,XX[10] and mos 48,XX,+mar × 2[72]/47,XX,+mar[28], respectively. The results of analyses of copy number variation (CNV) and fluorescence in situ hybridization (FISH) analyses, showed that the sSMCs were found to be idic(15) involving the Prader-Willi/Angelman Syndrome Critical Region (PWACR) genes and the P gene, with duplication sizes of 6.3 Mb and 9.7 Mb, respectively. DNA fingerprinting analysis of patient 1 showed a maternal origin for the idic(15). Both patients had mosaic idic(15) karyotypes: patient 1 had cells with a 15q partial octosomy (83%), and patient 2 had cells with a 15q partial hexasomy (72%).

Conclusions: We detected two rare mosaic idic(15) karyotypes that were associated with congenital abnormalities, including a rare mosaic octosomy of 15q11-q13. Our cases further validate the notion that the phenotypic severity is correlated with the level of mosaicism and the dosage effect of related genes in the proximal 15q.

Keywords: Developmental delay; Hyperpigmentation; Isodicentric 15; Mental retardation; P gene; Partial octosomy of 15q.

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Conflict of interest statement

This study was approved by the Institutional Ethics Committee of the Reproductive and Genetic Hospital of Citic-Xiangya, and written informed consent was obtained from all the participants prior to the genetic study.Written informed consent was obtained from the parents of the patients for the publication of this case report.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
The appearance, karyotyping, FISH and DNA fingerprinting results for patient 1. a Frontal view of patient 1 displays some facial dysmorphism, including ocular hypertelorism, nystagmus and uneven pigmentation. b Deeper pigmentation on the buttocks and back. c Partial karyotype by G-banding showing three extra idic(15) regions (red arrow) d FISH analysis using D15Z1 (green arrow) and D15S11 (red arrow) showing that each idic(15) has two green hybridization signals and two red hybridization signals. A normal chromosome 15 has one green and one red hybridization signal. e and f Electropherograms of the markers D15S156 (e) and D15S219 (f) in the father, children and mother (top to bottom). The children have three different alleles of D15S156 and D15S219. e The informative marker of D15S156 shows two different maternal alleles (206 and 224) and one paternal allele (212), indicating that the duplicated region of patient 1 was maternal. f The informative marker of D15S219 shows two different maternal alleles (308 and 310) and one paternal allele (299), again illustrating that the duplicated region was maternal
Fig. 2
Fig. 2
The appearance, karyotyping and FISH results for patient 2. a The proband has mild facial dysmorphism with low-set ears, a depressed nasal bridge and ocular hypertelorism. b Partial karyotype by G-banding showing two extra idic(15) regions (red arrow) c FISH analysis of patient 2 using whole-chromosome painting (WCP) probes showing one and two idic(15) regions d The patient 2 had a hemangioma (2 cm × 4 cm) on her left leg. e Partial karyotype by C-banding showing that each SMC(15) had two centromeres, indicating that the SMC(15) was idic(15)
Fig. 3
Fig. 3
SNP array analysis of both patients. A gain in copy number in the 15q11q13 region of patient 1 (left) and patient 2 (right). The orange box shows the location of the copy number gain on chromosome 15 in patient 1, and the blue box shows the location of the copy number gain on chromosome 15 in patient 2. The copy number was beyond the maximum limit of the software (4×). The values on the X-axis represent the log2 ratios for the patients
See this image and copyright information in PMC

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