Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment

Nagamani, Sandesh C. Sreenath; Zhang, Feng; Shchelochkov, Oleg A.; Bi, Weimin; Ou, Zhishuo; Scaglia, Fernando; Probst, Frank J.; Shinawi, Marwan; Eng, Christine M.; Hunter, Jill V.; Sparagana, Steven; Lagoe, Erin Caine; Fong, Chin To; Pearson, Margret; Doco‐Fenzy, Martine; Landais, Emilie; Mozelle, M; Chinault, A. Craig; Patel, Ankita; Bacino, Carlos A.; Sahoo, Trilochan; Kang, Si-Yong; Cheung, Sau-Wai; Lupski, James R.; Stankiewicz, Paweł

doi:10.1136/jmg.2009.067637

Cited by 106 publications

(44 citation statements)

References 33 publications

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“…We describe a recognisable but variable phenotype in eight individuals with microdeletions (table 5 and figure 3a) in 17p13.3 consistent with that recently described by Sreenath Nagamani et al 15 All individuals with 17p13.3 microdeletions had developmental delay of varying degree, except the patient in case 5, who had only mild learning difficulties, and the mother (6c) in cases 6a and 6b who, however, experienced transient speech problems as a young child. None displayed behavioural problems.…”

Section: Discussionsupporting

confidence: 87%

“…Owing to its function in the central nervous system,12 22 YWHAE is very likely to play a role in the phenotypes of the deletion patients. CRK is the likely candidate for growth restriction; notably, case 1 described by Sreenath Nagamani et al 15 and the single case described by Mignon-Ravix et al 13 showed neither growth restriction nor deletion of CRK (figure 1a and tables 2, 3 and 5). Benign CNVs within the deletion minimal overlapping region (MRO) have not been reported in a series of 891 healthy individuals (see Methods) nor in the Database of Genomic Variants (http://projects.tcag.ca/variation/) or the CHOP CNV Database (http://cnv.chop.edu/).…”

Section: Discussionmentioning

confidence: 93%

“…Bold type indicates common features among individuals with novel 17p13.3 microdeletions.*Sreenath Nagamani et al 15

–, not present; +, ++, present; ACC, agenesis of the corpus callosum; BHC, birth head circumference; BL, birth length; BW, birth weight; CP, cleft palate; DD, developmental delay; ILS, isolated lissencephaly sequence; LIS, lissencephaly; M, mean; MDS, Miller–Dieker syndrome; MR, mental retardation; N, normal; NI, no information; NP, not performed; PDA, persistent ductus arteriosus; PFO, persistent foramen ovale; VUR, vesico–urethral reflux.

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Section: Resultsmentioning

confidence: 99%

“…We are able to review and refine the molecular and clinical features of the recently described novel microdeletions13 15 and microduplications12 14 in chromosome 17p13.3 by describing eight and six new cases (including one sib pair), respectively. Comparing all 14 deletions, the delineated critical region spans approximately 258 kb (chr17: 1 136 270–1 394 633) and includes six genes (exons 2-3 of TUSC5 , YWHAE , CRK , MYO1C , SKIP and exons 1–4 of PITPNA ) (figure 1a).…”

Section: Discussionmentioning

confidence: 99%

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Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes

Bruno

Anderlid

Wedell

et al. 2010

Journal of Medical Genetics

143

181

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 93%

“…Bold type indicates common features among individuals with novel 17p13.3 microdeletions.*Sreenath Nagamani et al 15

…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes

Bruno

Anderlid

Wedell

et al. 2010

Journal of Medical Genetics

143

181

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“…Changes in 14-3-3ϵ dosage have been shown to alter neuronal migration, thereby impairing proper neurodevelopment [27]. Several studies have previously indicated that large duplications or deletions at 17p13.3 affecting this gene are associated with developmental delay or autism [20,28-30]. The small 24-kb duplication that we identified in our study has also been noted in our past work [31] and in clinical cohorts.…”

Section: Discussionsupporting

confidence: 84%

Copy number variation in Han Chinese individuals with autism spectrum disorder

Gazzellone

Zhou

Lionel

et al. 2014

J Neurodevelop Disord

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BackgroundAutism spectrum disorders (ASDs) are a group of neurodevelopmental conditions with a demonstrated genetic etiology. Rare (<1% frequency) copy number variations (CNVs) account for a proportion of the genetic events involved, but the contribution of these events in non-European ASD populations has not been well studied. Here, we report on rare CNVs detected in a cohort of individuals with ASD of Han Chinese background.MethodsDNA samples were obtained from 104 ASD probands and their parents who were recruited from Harbin, China. Samples were genotyped on the Affymetrix CytoScan HD platform. Rare CNVs were identified by comparing data with 873 technology-matched controls from Ontario and 1,235 additional population controls of Han Chinese ethnicity.ResultsOf the probands, 8.6% had at least 1 de novo CNV (overlapping the GIGYF2, SPRY1, 16p13.3, 16p11.2, 17p13.3-17p13.2, DMD, and NAP1L6 genes/loci). Rare inherited CNVs affected other plausible neurodevelopmental candidate genes including GRID2, LINGO2, and SLC39A12. A 24-kb duplication was also identified at YWHAE, a gene previously implicated in ASD and other developmental disorders. This duplication is observed at a similar frequency in cases and in population controls and is likely a benign Asian-specific copy number polymorphism.ConclusionsOur findings help define genomic features relevant to ASD in the Han Chinese and emphasize the importance of using ancestry-matched controls in medical genetic interpretations.

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Causes and Consequences of Structural Genomic Alterations in the Human Genome

Hart

O’Driscoll

2013

Encyclopedia of Life Sciences

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The revolutionary development and application of microarray‐based comparative genomic hybridisation (aCGH) technology within the past decade or so represents a profound and continuing fundamental contribution to the molecular dissection and characterisation of complex human disorders: disorders ranging from developmental pathologies including intellectual disability, schizophrenia and autism spectrum disorders to more common conditions such as cancer. A unifying underlying feature here is that these disorders are associated with complex structural rearrangements in chromosomes. aCGH technology application has also enabled the refinement of ‘old’ and identification of ‘new’ mechanisms to explain the origin of these complex chromosomal alterations. Interestingly, these structural variations can also incorporate genes whose products play fundamental roles in aspects of deoxyribonucleic acid repair, replication and recombination, thereby having an impact on genome‐wide stability and integrity. In this article, the mechanisms underlying complex structural chromosomal rearrangements are reviewed and their implications with respect to genome‐wide stability are discussed. Key Concepts: The locus‐specific frequency of CNVs are orders of magnitude higher than SNPs. CNVs are a significant contributor to human disease. CNVs can be recurrent or nonrecurrent. Nonallelic homologous recombination between low copy number repeats is a common mechanism of recurrent CNV. Nonhomologous end joining can underlie nonrecurrent CNVs. Complex Chromosomal Rearrangements (CCRs) are complex CNVs involving multiple contiguous changes in copy number. DNA replication based‐mechanisms have been invoked to explain CCRs. CNVs are fundamental contributors to cancer development and progression. CNVs incorporating genome instability pathway components can adversely impact on genome‐wide stability. Certain genomic disorders are characterised by impaired genome stability.

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Microdeletions including YWHAE in the Miller-Dieker syndrome region on chromosome 17p13.3 result in facial dysmorphisms, growth restriction, and cognitive impairment

Abstract: Microdeletions of chromosome 17p13.3 involving YWHAE present with growth restriction, craniofacial dysmorphisms, structural abnormalities of brain and cognitive impairment. The interstitial deletions are mediated by diverse molecular mechanisms.

Cited by 106 publications

References 33 publications

Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes

Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes

Copy number variation in Han Chinese individuals with autism spectrum disorder

Causes and Consequences of Structural Genomic Alterations in the Human Genome

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