Consistent chromosome abnormalities identify novel polymicrogyria loci in 1p36.3, 2p16.1–p23.1, 4q21.21–q22.1, 6q26–q27, and 21q2

Dobyns, William B.; Mirzaa, Ghayda; Christian, Susan L.; Petras, Kristin; Roseberry, Jessica A.; Clark, Gary D.; Curry, Cynthia J.; McDonald‐McGinn, Donna M.; Medne, Līvija; Zackai, Elaine H.; Parsons, Julie; Zand, Dina J.; Hisama, Fuki M.; Walsh, Christopher A.; Leventer, Richard J.; Martin, Christa Lese; Gajęcka, Marzena; Shaffer, Lisa G.

doi:10.1002/ajmg.a.32293

Cited by 100 publications

(104 citation statements)

References 114 publications

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“…In an analogous fashion several chromosomal loci have been proposed to underlie polymicrogyria [Dobyns et al, 2008] but here, in contrast to the situation with PH, the chromosomal associations have been recurrent and consistent, a finding more in keeping with a susceptibility conferred by hapolinsufficiency for one or a number of underlying genes in those regions. Of the described loci so far associated with PH, only duplications in 5p15 [Sheen et al, 2003] and deletions in 5q11 [Cardoso et al, 2009] may fulfill these criteria.…”

Section: Discussionmentioning

confidence: 78%

Periventricular Heterotopia in Common Microdeletion Syndromes

et al. 2010

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Periventricular heterotopia (PH) is a brain malformation characterised by heterotopic nodules of neurons lining the walls of the cerebral ventricles. Mutations in FLNA account for 20–24% of instances but a majority have no identifiable genetic aetiology. Often the co-occurrence of PH with a chromosomal anomaly is used to infer a new locus for a Mendelian form of PH. This study reports four PH patients with three different microdeletion syndromes, each characterised by high-resolution genomic microarray. In three patients the deletions at 1p36 and 22q11 are conventional in size, whilst a fourth child had a deletion at 7q11.23 that was larger in extent than is typically seen in Williams syndrome. Although some instances of PH associated with chromosomal deletions could be attributed to the unmasking of a recessive allele or be indicative of more prevalent subclinical migrational anomalies, the rarity of PH in these three microdeletion syndromes and the description of other non-recurrent chromosomal defects do suggest that PH may be a manifestation of multiple different forms of chromosomal imbalance. In many, but possibly not all, instances the co-occurrence of PH with a chromosomal deletion is not necessarily indicative of uncharacterised underlying monogenic loci for this particular neuronal migrational anomaly.

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Section: Discussionmentioning

confidence: 78%

Periventricular Heterotopia in Common Microdeletion Syndromes

et al. 2010

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“…PNH is considered a malformation of cortical development. Of note, other cortical malformations, that is polymicrogyria [Yao et al, 2006;Beri-Dexheimer et al, 2008;Dobyns et al, 2008] and lissencephaly [Miller et al, 2009], have been associated with 21q deletions. Yao et al [2006] propose that an 8.4-Mb region on 21q22.11-q22.3 is associated with cortical dysplasia.…”

Section: Discussionmentioning

confidence: 99%

Distinctive Phenotypic Abnormalities Associated with Submicroscopic 21q22 Deletion Including DYRK1A

Oegema¹,

Klein²,

Verkerk

et al. 2010

Mol Syndromol

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Partial monosomy 21 has been reported, but the phenotypes described are variable with location and size of the deletion. We present 2 patients with a partially overlapping microdeletion of 21q22 and a striking phenotypic resemblance. They both presented with severe psychomotor delay, behavioral problems, no speech, microcephaly, feeding problems with frequent regurgitation, idiopathic thrombocytopenia, obesity, deep set eyes, down turned corners of the mouth, dysplastic ears, and small chin. Brain MRI showed cerebral atrophy mostly evident in frontal and temporal lobes, widened ventricles and thin corpus callosum in both cases, and in one patient evidence of a migration disorder. The first patient also presented with epilepsy and a ventricular septum defect. The second patient had a unilateral Peters anomaly. Microarray analysis showed a partially overlapping microdeletion spanning about 2.5 Mb in the 21q22.1–q22.2 region including the DYRK1A gene and excluding RUNX1. These patients present with a recognizable phenotype specific for this 21q22.1–q22.2 locus. We searched the literature for patients with overlapping deletions including the DYRK1A gene, in order to define other genes responsible for this presentation.

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“…There are very few reports on patients with isolated de novo interstitial duplications partly overlapping with 2p14-p16.1 or 2p16.1-p22.1 and manifesting in mental retardation and variable dysmorphic features ( fig. 4 ) [Yunis et al, 1979;Say et al, 1980;Fryns et al, 1989;Parruti et al, 1989;Heathcote et al, 1991;Sawyer et al, 1994;Mégarbané et al, 1997;Dobyns et al, 2008;Guilherme et al, 2009]. In addition, molecular analysis was performed in very few previously reported cases [Dobyns et al, 2008;Guilherme et al, 2009], and the involvement of other chromosomal rearrangements could not be excluded.…”

Section: Discussionmentioning

confidence: 99%

“…4 ) [Yunis et al, 1979;Say et al, 1980;Fryns et al, 1989;Parruti et al, 1989;Heathcote et al, 1991;Sawyer et al, 1994;Mégarbané et al, 1997;Dobyns et al, 2008;Guilherme et al, 2009]. In addition, molecular analysis was performed in very few previously reported cases [Dobyns et al, 2008;Guilherme et al, 2009], and the involvement of other chromosomal rearrangements could not be excluded. Therefore, the detailed clinical and molecular presentation of the 2 new and rare cases of de novo interstitial duplications on chromosome 2p14-p22.1 in this report will provide a significant contribution to the scientific community.…”

Section: Discussionmentioning

confidence: 99%

Two New de novo Interstitial Duplications Covering 2p14–p22.1: Clinical and Molecular Analysis

Kasnauskienė¹,

Utkus²,

Čiuladaitė³

et al. 2012

Cytogenet Genome Res

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We provide a detailed clinical and molecular analysis of 2 patients with de novo interstitial duplications at 2p14–p16.1 and 2p16.1–p22.1. The 10.13-Mb duplication of chromosome 2p14–p16.1 was identified in a 9-year-old boy with mental retardation, behavioral problems (hyperactivity, hyperphagia, and subsequent vomiting), recurrent respiratory tract infections, macrocephaly, epilepsy, and dysmorphic features. The 17.49-Mb duplication of 2p16.1–p22.1 was found in a 17-year-old girl with moderate mental retardation, behavioral and emotional problems, anxiety, and facial dysmorphic features. Very few cases of de novo interstitial duplication of 2p14–p22.1 are reported in the literature, with the great majority of them lacking a detailed molecular analysis. The abnormal phenotype of these cases is caused by mechanisms such as the overdose of a duplicated gene (or genes), the disruption of a gene or its regulatory sequence by the breakpoints of duplication, or by an excess of genetic material which may disorganize chromatin conformation affecting distant gene expression. The clinical and molecular analysis of these 2 rare de novo interstitial duplications provides useful information which is extremely valuable for clinical evaluation at the prenatal and postnatal level and for the molecular understanding of the underlying mechanisms of human diseases.

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Consistent chromosome abnormalities identify novel polymicrogyria loci in 1p36.3, 2p16.1–p23.1, 4q21.21–q22.1, 6q26–q27, and 21q2

Cited by 100 publications

References 114 publications

Periventricular Heterotopia in Common Microdeletion Syndromes

Periventricular Heterotopia in Common Microdeletion Syndromes

Distinctive Phenotypic Abnormalities Associated with Submicroscopic 21q22 Deletion Including DYRK1A

Two New de novo Interstitial Duplications Covering 2p14–p22.1: Clinical and Molecular Analysis

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