6q27 subtelomeric deletions: Is there a specific phenotype?

Abstract

We read with great interest the report of Mosca et al. [2010] in theMay issue of the Journal, describing a patient with a 5.65Mb deletion on chromosome 6q27 (ranging from 165.24Mb to the 6q telomere at 170.89 Mb)associated with intellectual disability and a Ehlers–Danlos (EDS) like phenotype. We would like to further delineate the phenotypic spectrum of these rearrangements by reporting two additional patients with this chromosomal abnormality. Patient 1 is a 17-year-old girl, with a history of moderate psychomotor retardation, hypotonia and a sacral lipoma, that was surgically removed at age 5. She had mild dysmorphic features (downslanting, narrow palpebral fissures, a broad nasal root, malar hypoplasia, prominent ears, and thin vermillion of the upper lip). Brain MRI performed at age 16 as part of the investigations for the intellectual disability, showed an atypical cerebellar cyst, and evidence of periventricular nodular heterotopia. She has never had seizures

Delineation of candidate genes responsible for structural brain abnormalities in patients with terminal deletions of chromosome 6q27

“…[1][2][3][4][5][6][7][8][9]15,16 Though the clinical phenotypes associated with this deletion are quite variable, reports in unrelated subjects from independent investigators have shown that ACC, PNH, polymicrogyria, hydrocephalus, and cerebellar malformations are the consistently observed features. A recent analysis of a comprehensive map of loci for ACC from 374 patients revealed that chromosome 6q27 was one of the few loci wherein six or more subjects with ACC have been reported.…”

“…Structural brain malformations are consistently observed in these patients and include agenesis of the corpus callosum (ACC), periventricular nodular heterotopia (PNH), polymicrogyria, hydrocephalus, and cerebellar malformations. [1][2][3][4][5][6][7][8][9][10] Whereas previous studies have attempted to delineate the critical region responsible for brain malformations in patients with terminal 6q27 deletions, the sensitivity of the methodologies used has prevented the fine-mapping of the critical region. 1,6 A detailed genomic analysis of the subtelomeric chromosome 6q region would help identify the putative genes involved in the causation of brain malformations.…”

Genotype–Phenotype Correlations for Putative Haploinsufficient Genes in Deletions of 6q26-q27: Report of Eight Patients and Review of Literature

“…We also performed a literature review to evaluate the clinical and cytogenomic findings from 28 patients with a deletion of 6q26-q27. 12 13 14 15 16 17 18 19 20 21 22 23 24 25 From this series of 36 patients, we defined genotype–phenotype correlations from prenatal to postnatal stages and two critical regions with putative haploinsufficient genes and other candidate morbid genes. These results provided evidence for diagnostic interpretation, genetic counseling, and clinical management of patients with deletions of 6q26-q27.…”

Developmental Coordination Disorder in a Patient with Mental Disability and a Mild Phenotype Carrying Terminal 6q26-qter Deletion

“…Several authors have tried to correlate the distal deletion of chromosome 6q to a distinct clinical phenotype ( Stevenson et al, 2004 ; Bertini et al, 2006 ; Rigon et al, 2011 ; Zhou et al, 2014 ). Others have sought to identify the minimum deleted interval containing the critical genes responsible for the major clinical problems ( Eash et al, 2005 ; Rooms et al, 2006 ; Peddibhotla et al, 2015 ).…”

“…Others have sought to identify the minimum deleted interval containing the critical genes responsible for the major clinical problems ( Eash et al, 2005 ; Rooms et al, 2006 ; Peddibhotla et al, 2015 ). However, it is still very problematic to identify clinically patients carrying such deletion and to correlate deleted genes with a clinical phenotype ( Rigon et al, 2011 ).…”