2. Academic Validation
  3. Clinical phenotype of the recurrent 1q21.1 copy-number variant

Clinical phenotype of the recurrent 1q21.1 copy-number variant

  • Genet Med. 2016 Apr;18(4):341-9. doi: 10.1038/gim.2015.78.
Raphael Bernier 1,  Kyle J Steinman 2,  Beau Reilly 3,  Arianne Stevens Wallace 1,  Elliott H Sherr 4,  Nicholas Pojman 4,  Heather C Mefford 5,  Jennifer Gerdts 1,  Rachel Earl 1,  Ellen Hanson 6 7,  Robin P Goin-Kochel 8,  Leandra Berry 8,  Stephen Kanne 9,  LeeAnne Green Snyder 6 10,  Sarah Spence 11,  Melissa B Ramocki 12,  David W Evans 13,  John E Spiro 10,  Christa L Martin 13 14,  David H Ledbetter 13 14,  Wendy K Chung 15 16,  Simons VIP consortium
Affiliations

Affiliations

  • 1 Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington, USA.
  • 2 Department of Neurology, University of Washington, Seattle, Washington, USA.
  • 3 Lakeside Center for Autism, Issaquah, Washington, USA.
  • 4 Department of Neurology, University of California San Francisco, San Francisco, California, USA.
  • 5 Department of Pediatrics, University of Washington, Seattle, Washington, USA.
  • 6 Division of Developmental Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
  • 7 Harvard Medical School, Boston, Massachusetts, USA.
  • 8 Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
  • 9 Thompson Autism Center, University of Missouri, Columbia, Missouri, USA.
  • 10 Simons Foundation, New York, New York, USA.
  • 11 Department of Neurology, Boston Children's Hospital, Boston, Massachusetts, USA.
  • 12 Department of Neurology, Texas Children's Hospital, Houston, Texas, USA.
  • 13 Autism & Developmental Medicine Institute, Danville, Pennsylvania, USA.
  • 14 Genomic Medicine Institute, Geisinger Health System, Danville, Pennsylvania, USA.
  • 15 Department of Pediatrics, Columbia University, New York, New York, USA.
  • 16 Department of Medicine, Columbia University, New York, New York, USA.
PMID: 26066539 DOI: 10.1038/gim.2015.78
Abstract

Purpose: To characterize the clinical phenotype of the recurrent copy-number variation (CNV) at 1q21.1, we assessed the psychiatric and medical phenotypes of 1q21.1 deletion and duplication carriers ascertained through clinical genetic testing and family member cascade testing, with particular emphasis on dimensional assessment across multiple functional domains.

Methods: Nineteen individuals with 1q21.1 deletion, 19 individuals with the duplication, and 23 familial controls (noncarrier siblings and parents) spanning early childhood through adulthood were evaluated for psychiatric, neurologic, and other medical diagnoses, and their cognitive, adaptive, language, motor, and neurologic domains were also assessed. Twenty-eight individuals with 1q21.1 CNVs (15 deletion, 13 duplication) underwent structural magnetic resonance brain imaging.

Results: Probands with 1q21.1 CNVs presented with a range of psychiatric, neurologic, and medical disorders. Deletion and duplication carriers shared several features, including borderline cognitive functioning, impaired fine and gross motor functioning, articulation abnormalities, and hypotonia. Increased frequency of Autism Spectrum Disorder (ASD) diagnosis, increased ASD symptom severity, and increased prevalence of macrocephaly were observed in the duplication relative to deletion carriers, whereas reciprocally increased prevalence of microcephaly was observed in the deletion carriers.

Conclusions: Individuals with 1q21.1 deletions or duplications exhibit consistent deficits on motor and cognitive functioning and abnormalities in head circumference.Genet Med 18 4, 341-349.

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