A Rare Interstitial Duplication of 8q22.1–8q24.3 Associated with Syndromic Bilateral Cleft Lip/Palate

Abstract

We present a rare case of 8q interstitial duplication derived from maternal balanced translocations in a patient with bilateral cleft lip and palate in syndromic form associated with other congenital malformations. G-banding cytogenetic analysis revealed a chromosomal abnormality in the form of the karyotype 46,XX der(22)t(8;22)(q22.1;p11.1)mat. Chromosome microarray analysis evidenced a 49 Mb duplicated segment of chromosome 8q with no pathogenic imbalances on chromosome 22. Two siblings also carry the balanced translocation. We have compared this case with other “pure” trisomies of 8q patients reported in the literature and with genome wide association studies recently published. This work highlights the involvement of chromosome 8q in orofacial clefts.

Shared Neurodevelopmental Perturbations Can Lead to Intellectual Disability in Individuals with Distinct Rare Chromosome Duplications

“…ID is caused by perturbations in the significant biological functions that impact cellular networks present in different regions of the CNS. We identified the influence of each of the 44 prioritized genes ( Supplementary Table S5 ) in different tissues and found that these genes are mainly expressed in the CNS when compared with other tissues in humans ( Figure 3 ) [ 14 , 16 , 53 ].…”

“…Moreover, six genes from the duplicated region 18p11.32-p11.21 are highly expressed in several regions of the CNS, from which three of them (LAMA1, MYOM1, and TGIF1) were duplicated in individuals with ID [ 18 , 19 , 20 ]. Furthermore, patients with duplication of 8q24.13q24.3 region involving the KCNQ3, PTK2, ASAP1, and NDRG1 genes, which are widely expressed in CNS, presented ID [ 14 , 16 , 53 ].…”

“…Therefore, we used network analysis in an attempt to identify the potential sharing of biological processes and genes responsible for the pathophysiology of ID in rare duplications. We found seven candidate genes: PTK2 and KCNK3 (dup 8q24.13q24.3), LAMA1 (dup 18p11.32p11.21), and PAK3 , DCX , SOX3 , and OCRL from dupXq22.3q27, all duplicated in individuals with ID [ 15 , 16 , 19 , 23 , 25 , 55 , 56 , 57 , 61 ]. Furthermore, all candidate genes identified have been reported in duplicated regions of several ID patients in the web-based database—DECIPHER.…”

“…Moreover, the chromosome rearrangements identified in our patients are rare, with few cases reported so far. These duplicated regions have been reported as pathogenic and ID is a recurrent clinical finding in the affected individuals [ 16 , 21 , 26 ]. Therefore, we used network analysis in an attempt to identify the potential sharing of biological processes and genes responsible for the pathophysiology of ID in rare duplications.…”

“…Herein we determined whether genes located in duplicated regions in three patients followed up at our genetics service with rare but relevant regions (8q24.13q24.3, 18p11.32p11.21, and Xq22.3q27.2) are involved in shared central molecular pathways associated with genes related with ID. The 8q24.13q24.3 duplication identified is a rare chromosomal rearrangement associated with dysmorphic features, growth delay, and ID [ 13 , 14 , 15 , 16 ]. Moreover, variable levels of ID and cerebellum hypoplasia were described in patients with 18p11 duplications, however, few cases of pure duplications in this region have been reported with similar rearrangements so far [ 17 , 18 , 19 , 20 , 21 ].…”