Delineation of a de novo 7q21.3q31.1 Deletion by CGH-SNP Arrays in a Girl with Multiple Congenital Anomalies Including Severe Glaucoma

Abstract

In this study, we present a female patient with a constitutional de novo deletion in 7q21.3q31.1 as determined by G-banding and CGH-SNP arrays. She exhibited, among other features, psychomotor retardation, congenital severe bilateral glaucoma, a cleft palate, and heart defect. Microarray assay disclosed a deleted 12.5-Mb region roughly 88 kb downstream the ectrodactyly critical region; thus, the patient's final karyotype was 46,XX.arr 7q21.3q31.1(96,742,140- 109,246,085)×1 dn. This girl represents the fourth patient described so far with congenital glaucoma and a deletion encompassing or overlapping the 7q21.3q31.1 region, and confirms the presence of a locus or loci related to such a clinical feature. According to our results, the proneness to ocular defects secondary to 7q intermediate deletions could be caused by co-deletion of TAC1, HBP1, and a small cluster of cytochrome P450 genes (subfamily 3A). This conclusion is supported by their functional roles and expression locations as well as because TAC1 is related to the functional pathway of the MYOC gene whose mutations are linked to glaucoma. Moreover, given that this girl is clinically reminiscent of several phenotypes related to diverse deletions within 7q21q32, our results and observations offer a general overview of the gene content of deletions/phenotypes overlapping 7q21.3q31.1 and confirm that loci distal to DLX genes including the CUX1 gene and potential regulatory elements downstream from DLX5 are unrelated to ectrodactyly.

Interstitial deletion of 7q22.1q31.1 in a boy with structural brain abnormality, cardiac defect, developmental delay, and dysmorphic features

“…Our patient's deletion does not include SHFM1 , DLX5 , or DLX6 , the major candidates for ectrodactyly associated with intermediate 7q deletion (OMIM 129900) [Scherer et al, ; van Silfhout et al, ; Martínez‐Jacobo et al, ]. Correspondingly, our patient does not have ectrodactyly of the hands or feet.…”

“…1, Present Case; 2, Chen et al []; 3, Dirse et al []; 4, Al‐Hassnan et al []; 5, Uliana et al []; 6, Miller et al []; 7, Krepischi‐Santos et al []; 8, Martínez‐Jacobo et al []; 9, Rivera et al []; 10, Cheong et al []; 11, Ayraud et al []; 12, Morey and Higgins []; 13, Serup []; 14, Young et al [] (patient 5); 15, Dennis et al []; 16, Hull et al []; 17, Franceschini et al []; 18, Fagan et al [] (case 3); 19, Abuelo and Padre‐Mendoza []; 20, Manguoglu et al []; 21, Del Refugio Rivera‐Vega et al []; 22, Montgomery et al []; 23, Higginson et al []; 24, Klep‐de Pater et al [] (case 1); 25, Yilmaz et al []; 26, Kim et al []; 27, Zackowski et al []; 28, McElveen et al []; 29, Stallard and Juberg []; 30, Johnson et al []; 31, Pfeiffer []; 32, Valentine and Sergovich []; 33, Tajara et al []; 34, Chitayat et al [].…”

“…Interstitial deletions of chromosome 7q are relatively rare and are classified into three main categories according to which cytogenetic bands are involved: proximal (7q11 → q21), intermediate (7q21 → q32), and terminal (7q32 → qter) [Gibson et al, ; Young et al, ; Chitayat et al, ; Fagan et al, ; Tajara et al, ; Morey and Higgins, ; Zackowski et al, ; Yilmaz et al, ; Cheong et al, ; Martínez‐Jacobo et al, ; Kim et al, ; Del Refugio Rivera‐Vega et al, ]. Thirty‐three cases with partial deletions involving the 7q22q31 region have been described previously.…”

Copy number variants in Ebstein anomaly

“…Four CNVs were identified that overlapped or were close to transcription factors HES3 , TRIM71 , CUX1 and EIF4EBP2 which are important in cardiac development. HES3 and CUX1 have been reported to interact with Notch and Wnt pathways [ 22 , 23 ] and dysregulation of these signaling pathways is known to lead to congenital heart defects [ 24 , 25 ]. In case 1 a 22 Kb deletion was identified at 10q22.1, 19 Kb upstream of NODAL , which is a factor in cardiac progenitor differentiation [ 26 ] and an inducer of Sox17 , an endoderm-specific gene regulating paracrine signals in cardiogenesis [ 27 ].…”

Germline large genomic alterations on 7q in patients with multiple primary cancers

“…Deletions and cnLOH mapped on 7q have been widely described in both hematological malignancies; specifically myelodysplastic syndrome, acute myeloid leukemia (AML) and splenic marginal zone lymphoma 14 15 16 ; and BC 17 18 . Furthermore, genomic deletions on chromosome 7q have also been associated with congenital defects, including developmental delay, learning difficulties, craniofacial dysmorphism and hypogenitalism 19 20 21 22 .…”