Saethre–Chotzen phenotype with learning disability and hyper IgE phenotype in a patient due to complex chromosomal rearrangement involving chromosomes 3 and 7

Abstract

The authors describe on a Brazilian girl with coronal synostosis, facial asymmetry, ptosis, brachydactyly, significant learning difficulties, recurrent scalp infections with marked hair loss, and elevated serum immunoglobulin E. Standard lymphocyte karyotype showed a small additional segment in 7p21[46,XX,add(7)(p21)]. Deletion of the TWIST1 gene, detected by Multiplex Ligation Probe-dependent Amplification (MPLA) and array-CGH, was consistent with phenotype of Saethre-Chotzen syndrome. Array CGH also showed deletion of four other genes at 7p21.1 (SNX13, PRPS1L1, HD9C9, and FERD3L) and the deletion of six genes (CACNA2D2, C3orf18, HEMK1, CISH, MAPKAPK3, and DOCK3) at 3p21.31. Our case reinforces FERD3L as candidate gene for intellectual disability and suggested that genes located in 3p21.3 can be related to hyper IgE phenotype.

Microdeletions of 5.5 Mb (4q13.2–q13.3) and 4.1 Mb (7p15.3–p21.1) associated with a saethre–chotzen‐like phenotype, severe intellectual disability, and autism

“…In comparison, extremely severe intellectual disability was evident in the present patient despite a smaller deletion of 5.5 Mb, as evidenced by immobility and speech impairment. The effect of the 5.5 Mb deletion is probably modified by the concurrent deletion at 4q13.2–q13.3, analogous to that of a previously reported patient, in whom a concurrent 3p21.31 microdeletion with a size of 356 kb was detected [Zechi‐Ceide et al, ].…”

“…For example, Fer3‐like protein gene ( FERD3L ), encoding a 166 AA helix–loop–helix protein, is expressed in the developing central nervous system [Schluth‐Bolard et al, ]. Similarly, histone deacetylase 9 gene ( HDAC9 ), which regulates transcription by histone modification, can also be considered relevant for brain development [Zechi‐Ceide et al, ]. Both these genes are within the deleted chromosomal regions in the present patient.…”

Transcriptome profiling reveals expression signatures of cranial neural crest cells arising from different axial levels

“…Moreover, identification of genes previously found enriched in NCCs arising anterior to r3 provides confidence that our dataset uncovers genetic networks underlying the diversity of NCCs arising at different axial levels. Amongst the other transcription factors specific to the r1-r2 stream Ferd3l has also been implicated in the craniofacial disorder Saethre-Chotzen syndrome [51], however, the remaining transcription factors have unknown roles in cranial NCCs. Sp8 and Sp9 are both members of the Sp/KLF transcription factor family that have essential roles in organising craniofacial, limb and interneuron development [52, 53].…”

Y‐craniosynostosis by premature fusion of the metopic and coronal sutures: A new nosological entity or a variety of Saethre‐Chotzen syndrome?

“…It was hypothesized that the microdeletion in 7p21.1 was a contiguous gene syndrome, with TWIST1 being responsible for the craniosynostosis and other gene(s) accounting for mental disability. Indeed, it has been suggested that deletions of the flanking gene of TWIST1, FERD3L (RefSeqNM_152898), contribute to significant developmental delay (Zechi‐Ceide et al, ). This gene is, in fact, expressed during the developing central nervous system (Segev et al, ; Verzi et al, ).…”