A rare familial rearrangement of chromosomes 9 and 15 associated with intellectual disability: a clinical and molecular study

Natalya A Lemskaya,Asia R Shorina,Dmitry V Yudkin,Polina L Perelman,Elena A Filimonova,Alexander A Dolskiy,Dmitry Yu Prokopov,Mariia A Rezakova,Svetlana A Romanenko,Yulia V Maksimova

doi:10.1186/s13039-021-00565-y

Abstract

BackgroundThere are many reports on rearrangements occurring separately in the regions of chromosomes 9p and 15q affected in the case under study. 15q duplication syndrome is caused by the presence of at least one extra maternally derived copy of the Prader–Willi/Angelman critical region. Trisomy 9p is the fourth most frequent chromosome anomaly with a clinically recognizable syndrome often accompanied by intellectual disability. Here we report a new case of a patient with maternally derived unique complex sSMC resulting in partial trisomy of both chromosomes 9 and 15 associated with intellectual disability.Case presentationWe characterise a supernumerary derivative chromosome 15: 47,XY,+der(15)t(9;15)(p21.2;q13.2), likely resulting from 3:1 malsegregation during maternal gametogenesis. Chromosomal analysis showed that a phenotypically normal mother is a carrier of balanced translocation t(9;15)(p21.1;q13.2). Her 7-year-old son showed signs of intellectual disability and a number of physical abnormalities including bilateral cryptorchidism and congenital megaureter. The child’s magnetic resonance imaging showed changes in brain volume and in structural and functional connectivity revealing phenotypic changes caused by the presence of the extra chromosome material, whereas the mother’s brain MRI was normal. Sequence analyses of the microdissected der(15) chromosome detected two breakpoint regions: HSA9:25,928,021-26,157,441 (9p21.2 band) and HSA15:30,552,104-30,765,905 (15q13.2 band). The breakpoint region on chromosome HSA9 is poor in genetic features with several areas of high homology with the breakpoint region on chromosome 15. The breakpoint region on HSA15 is located in the area of a large segmental duplication.ConclusionsWe discuss the case of these phenotypic and brain MRI features in light of reported signatures for 9p partial trisomy and 15 duplication syndromes and analyze how the genomic characteristics of the found breakpoint regions have contributed to the origin of the derivative chromosome. We recommend MRI for all patients with a developmental delay, especially in cases with identified rearrangements, to accumulate more information on brain phenotypes related to chromosomal syndromes.

Highlights

There are many reports on rearrangements occurring separately in the regions of chromosomes 9p and 15q affected in the case under study. 15q duplication syndrome is caused by the presence of at least one extra maternally derived copy of the Prader–Willi/Angelman critical region
We recommend magnetic resonance imaging (MRI) for all patients with a developmental delay, especially in cases with identified rearrangements, to accumulate more information on brain phenotypes related to chromosomal syndromes
We describe a boy with a developmental delay and a complex small supernumerary marker chromosomes (sSMCs) arising from a 3:1 segregation error of a maternally derived translocation between chromosome 15q13.2 and chromosome 9p21.2, which led to trisomy of chromosome 15pter-q13.2 and 9pter-9p21.2

Summary

Introduction

There are many reports on rearrangements occurring separately in the regions of chromosomes 9p and 15q affected in the case under study. 15q duplication syndrome is caused by the presence of at least one extra maternally derived copy of the Prader–Willi/Angelman critical region. We report a new case of a patient with maternally derived unique complex sSMC resulting in partial trisomy of both chromosomes 9 and 15 associated with intellectual disability. Chromosomal analysis showed that a phenotypically normal mother is a carrier of balanced translocation t(9;15)(p21.1;q13.2). Her 7-year-old son showed signs of intellectual disability and a number of physical abnormalities including bilateral cryptorchidism and congenital megaureter. A subset of rare small supernumerary marker chromosomes (sSMCs) consists of the material from two or three chromosomes as a result of meiotic malsegregation in carriers of a balanced reciprocal or Robertsonian translocation [1]. Conventional karyotyping can certainly identify the presence of large balanced chromosomal aberrations, origin identification for small supernumerary elements is beyond its resolution. Breakpoints of chromosomal rearrangements are important for identifying and revealing an underlying gene function, an understanding of the mechanisms leading to chromosome rearrangements, and finding common features for breakpoint regions

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