Genotype-phenotype analysis of recombinant chromosome 4 syndrome: an array-CGH study and literature review

Abstract

BackgroundRecombinant chromosome 4, a rare constitutional rearrangement arising from pericentric inversion, comprises a duplicated segment of 4p13~p15→4pter and a deleted segment of 4q35→4qter. To date, 10 cases of recombinant chromosome 4 have been reported.ResultWe describe the second case in which array-CGH was used to characterize recombinant chromosome 4 syndrome. The patient was a one-year old boy with consistent clinical features. Conventional cytogenetics and FISH documented a recombinant chromosome 4, derived from a paternal pericentric inversion, leading to partial trisomy 4p and partial monosomy of 4q. Array-CGH, performed to further characterize the rearranged chromosome 4 and delineate the breakpoints, documented a small (4.36 Mb) 4q35.1 terminal deletion and a large (23.81 Mb) 4p15.1 terminal duplication. Genotype-phenotype analysis of 10 previously reported cases and the present case indicated relatively consistent clinical features and breakpoints. This consistency was more evident in our case and another characterized by array-CGH, where both showed the common breakpoints of p15.1 and q35.1. A genotype-phenotype correlation study between rec(4), dup(4p), and del(4q) syndromes revealed that urogenital and cardiac defects are probably due to the deletion of 4q whereas the other clinical features are likely due to 4p duplication.ConclusionOur findings support that the clinical features of patients with rec(4) are relatively consistent and specific to the regions of duplication or deletion. Recombinant chromosome 4 syndrome thus appears to be a discrete entity that can be suspected on the basis of clinical features or specific deleted and duplicated chromosomal regions.

Analyses of Genotypes and Phenotypes of Ten Chinese Patients with Wolf-Hirschhorn Syndrome by Multiplex Ligation-dependent Probe Amplification and Array Comparative Genomic Hybridization

“…[ 1 2 ] The WHS patients have been examined by novel technologies, such as array comparative genomic hybridization (array CGH) and multiplex ligation-dependent probe amplification (MLPA). [ 3 4 ] Array CGH enables the detection of the precise sizes of deletions in the WHS candidate region (WHSCR) with greater accuracy compared with either fluorescence in situ hybridization (FISH) or conventional G-banded chromosome analysis alone. [ 5 ] In addition, MLPA allows for a more comprehensive determination of gene dosages with increased convenience and a relatively low cost compared with subtelomeric FISH analysis.…”

Bir Rekombinant Kromozom 4 Olgusunun Klinik Özelliklerinin Ayrıntılı Tanımlanması

“…Except for our case only one case in the literature has been reported to be de novo [4]. FISH was only performed to four of all reported cases [8][9][10] and only two of them were confirmed with array CGH [9][10]. According the literature, all cases have the same or very close breakpoints, within sub-bands p13~p15 and q35 ( Table 1).…”

“…We reported a case with de novo recombinant chromosome 4 which had the largest deletion and duplication in the literature, to the best of our knowledge, in this clinical report. Recombination of chromosome 4 is a very rare event with eighteen reported cases in the literature up to date [1][2][3][4][5][6][7][8][9][10]. Ten of them were because of parental pericentric inversions of chromosome 4 (6 paternal/ 4 maternal).…”

“…Recombinant chromosome 4 is a very rare chromosomal aberration with eighteen cases reported in the literature up to date [1][2][3][4][5][6][7][8][9][10][11]. All of the reported cases are due to parental pericentric inversion of chromosome 4.…”

Molecular cytogenetic characterization of a 2q35‐q37 duplication and a 4q35.1‐q35.2 deletion in two cousins: A genotype–phenotype analysis

“…With respect to 4q3 terminal deletion syndrome, patients with this condition display variable phenotypes that correlate with the extent and mapping of the rearranged region. Common clinical features include intellectual disability, a wide variety of head and facial abnormalities such as hypertelorism, malformed ears, cleft palate, short nose, congenital heart, and genitourinary defects [Maurin et al, ; Rashidi‐Nezhad et al, ; Strehle et al, ; Hemmat et al, ]. A number of cases of 4q deletion overlapping the 4q35.1‐q35.2 region have been reported: few of these have been isolated terminal 4q deletions, while the majority of patients also exhibited additional chromosomal rearrangements [Descartes et al, ; Tsai et al, ; Van Buggenhout et al, ; Cingoz et al, ; Vogt et al, ; Bendavid et al, ; Connel et al, ; Quadrelli et al, ; Bartholdi et al, ; Kaalund et al, ; Kitsiou‐Tzeli et al, ; Russel et al, ; Sensi et al, ; Maurin et al, ; Rossi et al, ; Chien et al, ; Markiewicz et al, ; Khalifa et al, ; Hemmat et al, ; Vona et al, ] (Fig.…”