Clinical phenotype and molecular characterization of 6q terminal deletion syndrome: Five new cases

Striano, Pasquale; Malacarne, Michela; Cavani, Simona; Pierluigi, Mauro; Rinaldi, Rosanna; Cavaliere, Maria Luigia; Rinaldi, Maria Michela; Bernardo, Carmelilia De; Coppola, Antonietta; Pintaudi, Maria; Gaggero, R.; Grammatico, Paola; Striano, Salvatore; Dallapiccola, Bruno; Zara, Federico; Faravelli, Francesca

doi:10.1002/ajmg.a.31435

Cited by 45 publications

(40 citation statements)

References 20 publications

(38 reference statements)

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“…Our patients displayed only mild joint laxity (which is likely related to hypotonia rather than to a connective tissue abnormality). Both had 6q27 deletions smaller than the one detected in the patient of Mosca et al [2010] (5.65 Mb); however deletion size also in this case is apparently unrelated to the presence of EDS-like features since the two patients published by Bertini et al [2006] and three out of five patients of Striano et al [2006] had deletions larger than 6 Mb but apparently lacked features of EDS.…”

contrasting

confidence: 48%

6q27 subtelomeric deletions: Is there a specific phenotype?

Rigon

Salviati

Mandarano

et al. 2011

American J of Med Genetics Pt A

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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

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contrasting

confidence: 48%

6q27 subtelomeric deletions: Is there a specific phenotype?

Rigon

Salviati

Mandarano

et al. 2011

American J of Med Genetics Pt A

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“…[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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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Patients with terminal deletions of chromosome 6q present with structural brain abnormalities including agenesis of corpus callosum, hydrocephalus, periventricular nodular heterotopia, and cerebellar malformations. The 6q27 region harbors genes that are important for the normal development of brain and delineation of a critical deletion region for structural brain abnormalities may lead to a better genotype-phenotype correlation. We conducted a detailed clinical and molecular characterization of seven unrelated patients with deletions involving chromosome 6q27. All patients had structural brain abnormalities. Using array comparative genomic hybridization, we mapped the size, extent, and genomic content of these deletions. The smallest region of overlap spans 1.7 Mb and contains DLL1, THBS2, PHF10, and C6orf70 (ERMARD) that are plausible candidates for the causation of structural brain abnormalities. Our study reiterates the importance of 6q27 region in normal development of brain and helps identify putative genes in causation of structural brain anomalies.

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“…Both deletions were the two largest deletions in our sample, exceeding 10 Mb. Epilepsy in 6q terminal deletion syndrome is a welldescribed feature, 16,17 whereas intellectual disability is usually the most prominent feature in 3p deletion syndrome. 18,19 As parents were not available for a significant proportion of patients, the frequency of de novo variants might be an underestimation.…”

Section: Discussionmentioning

confidence: 99%

Structural genomic variation in childhood epilepsies with complex phenotypes

et al. 2013

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A genetic contribution to a broad range of epilepsies has been postulated, and particularly copy number variations (CNVs) have emerged as significant genetic risk factors. However, the role of CNVs in patients with epilepsies with complex phenotypes is not known. Therefore, we investigated the role of CNVs in patients with unclassified epilepsies and complex phenotypes. A total of 222 patients from three European countries, including patients with structural lesions on magnetic resonance imaging (MRI), dysmorphic features, and multiple congenital anomalies, were clinically evaluated and screened for CNVs. MRI findings including acquired or developmental lesions and patient characteristics were subdivided and analyzed in subgroups. MRI data were available for 88.3% of patients, of whom 41.6% had abnormal MRI findings. Eighty-eight rare CNVs were discovered in 71 out of 222 patients (31.9%). Segregation of all identified variants could be assessed in 42 patients, 11 of which were de novo. The frequency of all structural variants and de novo variants was not statistically different between patients with or without MRI abnormalities or MRI subcategories. Patients with dysmorphic features were more likely to carry a rare CNV. Genome-wide screening methods for rare CNVs may provide clues for the genetic etiology in patients with a broader range of epilepsies than previously anticipated, including in patients with various brain anomalies detectable by MRI. Performing genome-wide screens for rare CNVs can be a valuable contribution to the routine diagnostic workup in patients with a broad range of childhood epilepsies.

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Clinical phenotype and molecular characterization of 6q terminal deletion syndrome: Five new cases

Cited by 45 publications

References 20 publications

6q27 subtelomeric deletions: Is there a specific phenotype?

6q27 subtelomeric deletions: Is there a specific phenotype?

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

Structural genomic variation in childhood epilepsies with complex phenotypes

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