Patients Carrying 9q31.1-q32 Deletion Share Common Features with Cornelia de Lange Syndrome

Abstract

Background: Cornelia de Lange Syndrome (CdLS) is a rare but severe clinically heterogeneous developmental disorder characterized by facial dysmorphia, growth and cognitive retardation, and abnormalities of limb development. Objectives: To determine the pathogenesis of a patient with CdLS. Methods: We studied a patient with CdLS by whole exome sequencing, karyotyping and Agilent CGH Array. The results were confirmed by quantitative real-time PCR analysis of the patient and her parents. Further comparison of our patient and cases with partially overlapping deletions retrieved from the literature and databases was undertaken. Results: Whole exome sequencing had excluded the mutation of cohesion genes such as NIPBL,SMC1A and SMC3. The result of karyotyping showed a deletion of chromosome 9q31.1-q32 and the result of Agilent CGH Array further displayed a 12.01-Mb region of deletion at chromosome bands 9q31.1-q32. Reported cases with the deletion of 9q31.1-q32 share similar features with our CdLS patient. One of the genes in the deleted region, SMC2, belongs to the Structural Maintenance of Chromosomes (SMC) family and regulates gene expression and DNA repair. Conclusions: Patients carrying the deletion of 9q31.1-q32 showed similar phenotypes with CdLS.

A novel familial 9q31.2q32 microdeletion: Muscle cramping, somnolence, fatigue, sensorineural hearing loss, pubertal delay, and short stature

“…Most of these were detected using conventional chromosome banding analysis, and to date, no clear syndrome has been identified). Seven cases have currently been reported using CMA techniques with precise breakpoints that overlap the 9q31.2q32 region . These are represented graphically in Figure and aligned against the deletion seen in our cohort, with a summary of the clinical reports available in Table .…”

“…Seven cases have currently been reported using CMA techniques with precise breakpoints that overlap the 9q31.2q32 region. [9][10][11][12][13] These are represented graphically in Figure 3 and aligned against the deletion seen in our cohort, with a summary of the clinical reports available in Table 2. A critical overlapping area extends from chr9: 109711873-113407621 (hg18).…”

“…This patient had the features of KBG syndrome (OMIM 148050). Cao et al described a patient with a 12.1 Mb deletion involving chromosome region 9q31.1q32 (chr9: 106898551, converted to hg18 from hg19) with sensorineural hearing loss, poor growth, delayed motor milestones, and dysmorphic facial features. Comparison was made between this patient's phenotype and the clinical features of Cornelia de Lange syndrome (CdLS, OMIM 122470).…”

Delineation of the 9q31 deletion syndrome: Genomic microarray characterization of two patients with overlapping deletions

“…Interstitial deletions of chromosome 9q from band 9q21 to 9q34 represent a very rare condition with only 23 patients described to date (Cao et al, ; Chien et al, ; Gamerdinger, Eggermann, Schubert, Schwanitz, & Kreiss‐Nachtsheim, ; Kulharya et al, ; Mucciolo et al, ; van Bon et al, ; Xu et al, ).…”

Response to Dylan Mordaunt and Alisha McLauchlan

“…In conclusion, CdLS shows a large spectrum of phenotypic heterogeneity and although generalizations may be helpful for clinicians we are also aware that these should be taken cautiously. Recent identification of several new genes and genetic mechanisms in CdLS or CdLS-like patients will no doubt add to the phenotypic and genotypic heterogeneity of cohesinopathies (12)(13)(14)(15)(16)(17)(18)(19).…”