Cerebellar and posterior fossa malformations in patients with autism‐associated chromosome 22q13 terminal deletion12. Issue 1 (7th December 2012)

• Record Type: Journal Article
• Authors: Aldinger, Kimberly A.; Kogan, Jillene; Kimonis, Virginia; Fernandez, Bridget; Horn, Denise; Klopocki, Eva; Chung, Brian; Toutain, Annick; Weksberg, Rosanna; Millen, Kathleen J.; Barkovich, A. James; Dobyns, William B.
• Is Part Of: American journal of medical genetics. Volume 161:Issue 1(2013:Jan.)
• Page Start: 131
• Page End: 136
• Publication Date: 2012-12-07
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.35700
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The 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 <italic>SHANK3</italic> mutation. We report the first brain‐imaging data showing that some patients with 22q13 deletions have severe posterior CBVH, and one individual with a <italic>SHANK3</italic> 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 <italic>SHANK3</italic> disruption. Other genes in the region, including <italic>PLXNB2</italic> and <italic>MAPK8IP2</italic>, 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. © 2012 Wiley Periodicals, Inc.</p> </abstract>