Duplication 9p and their implication to phenotype

Abstract

BackgroundTrisomy 9p is one of the most common partial trisomies found in newborns. We report the clinical features and cytogenomic findings in five patients with different chromosome rearrangements resulting in complete 9p duplication, three of them involving 9p centromere alterations.MethodsThe rearrangements in the patients were characterized by G-banding, SNP-array and fluorescent in situ hybridization (FISH) with different probes.ResultsTwo patients presented de novo dicentric chromosomes: der(9;15)t(9;15)(p11.2;p13) and der(9;21)t(9;21)(p13.1;p13.1). One patient presented two concomitant rearranged chromosomes: a der(12)t(9;12)(q21.13;p13.33) and an psu i(9)(p10) which showed FISH centromeric signal smaller than in the normal chromosome 9. Besides the duplication 9p24.3p13.1, array revealed a 7.3 Mb deletion in 9q13q21.13 in this patient. The break in the psu i(9)(p10) probably occurred in the centromere resulting in a smaller centromere and with part of the 9q translocated to the distal 12p with the deletion 9q occurring during this rearrangement. Two patients, brother and sister, present 9p duplication concomitant to 18p deletion due to an inherited der(18)t(9;18)(p11.2;p11.31)mat.ConclusionsThe patients with trisomy 9p present a well-recognizable phenotype due to facial appearance, although the genotype-phenotype correlation can be difficult due to concomitant partial monosomy of other chromosomes. The chromosome 9 is rich in segmental duplication, especially in pericentromeric region, with high degree of sequence identity to sequences in 15p, 18p and 21p, chromosomes involved in our rearrangements. Thus, we suggest that chromosome 9 is prone to illegitimate recombination, either intrachromosomal or interchromosomal, which predisposes it to rearrangements, frequently involving pericentromeric regions.

Application of high-resolution array comparative genomic hybridization in children with unknown syndromic microcephaly

“…In 16 out of the 25 patients with unknown microcephaly and CNV findings (Table 1b) we identified genes which could potentially play a significant role in small head circumference. From a total of 21 candidate genes, only 6 (FREM1, SOX1, ARHGEF7, EHMT1, CHD5, RE(RE)) have been previously reported to be involved in brain deficit causing microcephaly (Table 1b and Table 2) (8)(9)(10)(11)(12)(13).…”

Trisomy 9p. A brief clinical, diagnostic and therapeutic description

“…In most cases, partial trisomy 9p occurs as a result of parental reciprocal translocation between chromosome 9 and other autosome. 2,3,8 Therefore, phenotypic heterogeneity is correlated to the variable size of the duplicated segment (producing trisomy 9p) and the monosomy of the other chromosomal segment. 3,4,8 To a lower extent, it is the result of a spontaneous (de novo) genetic alteration occurring for unknown reasons during early embryonic development, i.e., it is not passed by any of the parents.…”

“…2,3,8 Therefore, phenotypic heterogeneity is correlated to the variable size of the duplicated segment (producing trisomy 9p) and the monosomy of the other chromosomal segment. 3,4,8 To a lower extent, it is the result of a spontaneous (de novo) genetic alteration occurring for unknown reasons during early embryonic development, i.e., it is not passed by any of the parents. 2,8 Based on the aforementioned information, e s t a b l i s h i n g t h e g e n o t y p e -p h e n o t y p e correlation may be hindered by the presence of small deletions or duplications affecting other chromosomes in most reported cases of trisomy 9p.…”

“…1 A potential explanation may be that this is a relatively poor gene region, so it may be more compatible with survival. [1][2][3] Trisomy 9p accounts for the fourth most frequent autosomal trisomy, after trisomies 21, 18, and 13. 2,4 It was first described in 4 patients by Rethoré et al in 1970 [1][2][3][4][5] and then outlined by Centerwall and Beatty-DeSana in 1975.…”

“…4 It is a clinically recognizable entity and, to date, more than 200 cases have been reported in the bibliography. [1][2][3][4][5][6] It is characterized by the complete (Figure 1) or partial duplication of 9p. 2 Treatment with recombinant human growth hormone may be considered in patients with trisomy 9p with short stature, while taking into account the severity of intellectual disability and the potential for social inclusion.…”