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Article: Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion

TitleCerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion
Authors
KeywordsCerebellum
Chromosome
Deletion
SHANK3
Issue Date2013
PublisherJohn Wiley & Sons, Inc.
Citation
American Journal of Medical Genetics, Part A, 2013, v. 161 n. 1, p. 131-136 How to Cite?
AbstractThe 22q13.3 deletion causes a neurodevelopmental syndrome, also known as Phelan-McDermid syndrome (MIM #606232), characterized by developmental delay and severe delay or absence of expressive speech. Two patients with hemizygous chromosome 22q13.3 telomeric deletion were referred to us when brain-imaging studies revealed cerebellar vermis hypoplasia (CBVH). To determine whether developmental abnormalities of the cerebellum are a consistent feature of the 22q13.3 deletion syndrome, we examined brain-imaging studies for 10 unrelated subjects with 22q13 terminal deletion. In seven cases where the availability of DNA and array technology allowed, we mapped deletion boundaries using comparative intensity analysis with single nucleotide polymorphism (SNP) microarrays. Approximate deletion boundaries for three additional cases were derived from clinical or published molecular data. We also examined brain-imaging studies for a patient with an intragenic SHANK3 mutation. We report the first brain-imaging data showing that some patients with 22q13 deletions have severe posterior CBVH, and one individual with a SHANK3 mutation has a normal cerebellum. This genotype-phenotype study suggests that the 22q13 deletion phenotype includes abnormal posterior fossa structures that are unlikely to be attributed to SHANK3 disruption. Other genes in the region, including PLXNB2 and MAPK8IP2, display brain expression patterns and mouse mutant phenotypes critical for proper cerebellar development. Future studies of these genes may elucidate their relationship to 22q13.3 deletion phenotypes. (c) 2012 Wiley Periodicals, Inc.
DescriptionResearch article
Persistent Identifierhttp://hdl.handle.net/10722/180153
ISSN
2015 Impact Factor: 2.082
2015 SCImago Journal Rankings: 1.115
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorAldinger, KAen_US
dc.contributor.authorKogan, Jen_US
dc.contributor.authorKimonis, Ven_US
dc.contributor.authorFernandez, Ben_US
dc.contributor.authorHorn, Den_US
dc.contributor.authorKlopocki, Een_US
dc.contributor.authorChung, Ben_US
dc.contributor.authorToutain, Aen_US
dc.contributor.authorWeksberg, Ren_US
dc.contributor.authorMillen, KJen_US
dc.contributor.authorBarkovich, AJen_US
dc.contributor.authorDobyns, WBen_US
dc.date.accessioned2013-01-21T01:30:56Z-
dc.date.available2013-01-21T01:30:56Z-
dc.date.issued2013en_US
dc.identifier.citationAmerican Journal of Medical Genetics, Part A, 2013, v. 161 n. 1, p. 131-136en_US
dc.identifier.issn1552-4825-
dc.identifier.urihttp://hdl.handle.net/10722/180153-
dc.descriptionResearch article-
dc.description.abstractThe 22q13.3 deletion causes a neurodevelopmental syndrome, also known as Phelan-McDermid syndrome (MIM #606232), characterized by developmental delay and severe delay or absence of expressive speech. Two patients with hemizygous chromosome 22q13.3 telomeric deletion were referred to us when brain-imaging studies revealed cerebellar vermis hypoplasia (CBVH). To determine whether developmental abnormalities of the cerebellum are a consistent feature of the 22q13.3 deletion syndrome, we examined brain-imaging studies for 10 unrelated subjects with 22q13 terminal deletion. In seven cases where the availability of DNA and array technology allowed, we mapped deletion boundaries using comparative intensity analysis with single nucleotide polymorphism (SNP) microarrays. Approximate deletion boundaries for three additional cases were derived from clinical or published molecular data. We also examined brain-imaging studies for a patient with an intragenic SHANK3 mutation. We report the first brain-imaging data showing that some patients with 22q13 deletions have severe posterior CBVH, and one individual with a SHANK3 mutation has a normal cerebellum. This genotype-phenotype study suggests that the 22q13 deletion phenotype includes abnormal posterior fossa structures that are unlikely to be attributed to SHANK3 disruption. Other genes in the region, including PLXNB2 and MAPK8IP2, display brain expression patterns and mouse mutant phenotypes critical for proper cerebellar development. Future studies of these genes may elucidate their relationship to 22q13.3 deletion phenotypes. (c) 2012 Wiley Periodicals, Inc.-
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc.-
dc.relation.ispartofAmerican Journal of Medical Genetics, Part Aen_US
dc.rightsAmerican Journal of Medical Genetics, Part A. Copyright © John Wiley & Sons, Inc.-
dc.subjectCerebellum-
dc.subjectChromosome-
dc.subjectDeletion-
dc.subjectSHANK3-
dc.titleCerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletionen_US
dc.typeArticleen_US
dc.identifier.emailChung, B: bhychung@hku.hken_US
dc.identifier.emailDobyns, WB: wbd@wu.edu-
dc.identifier.authorityChung, B=rp00473en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1002/ajmg.a.35700-
dc.identifier.pmid23225497-
dc.identifier.scopuseid_2-s2.0-84871680197-
dc.identifier.hkuros213000en_US
dc.identifier.volume161en_US
dc.identifier.issue1-
dc.identifier.spage131en_US
dc.identifier.epage136en_US
dc.identifier.isiWOS:000312939200021-
dc.publisher.placeUnited States-

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