Intragenic CAMTA1 deletions are associated with a spectrum of neurobehavioral phenotypes

2014-04-17 13:51:16

Clinical Genetics; 2014 April 17; DOI:10.1111/cge.12407

Marwan Shinawi, Rohini Coorg, Joshua Shimony, Dorothy K. Grange, Hussam Al-Kateb


Intragenic copy number variations involving the calmodulin-binding transcription activator 1 (CAMTA1) gene have recently been reported in four unrelated families with intellectual disability (ID), ataxia, behavioral- and cerebellar abnormalities.

We report a detailed phenotypic and molecular characterization of three individuals with novel intragenic CAMTA1 deletions from two unrelated families and compare the findings to those of previously reported patients.

Our patients had deletions of exons 6-11 and presented with ID, developmental delay (DD), attention deficit hyperactivity disorder (ADHD) and constipation. Two individuals from one family had also unsteady gait. Consistent phenotypes associated with CAMTA1 intragenic rearrangements include ID, speech problems and some dysmorphic features whereas neurobehavioral abnormalities are variable. We did not observe obvious phenotypic differences between patients with in-frame and those with frameshift rearrangements.

There is increased evidence that CAMTA1 has a role in brain and cerebellar function. CAMTA1 should be added to the growing list of genes associated with ID/DD, especially when behavioral problems, cerebellar signs, and/or dysmorphism are also present.


The diagnostic yield of genome-wide array analysis in patients with ID/DD can reach up to 20%. The improved resolution of whole-genome arrays has enabled the detection of small intragenic rearrangements, and allowed disease gene discovery and a better delineation of the genotype-phenotype correlation.

Recently, heterozygous intragenic rearrangements in the CAMTA1 gene were associated with ID and cerebellar ataxia. One patient had a de novo 305 kb deletion encompassing three genes as well as the promoter region and the first three exons of the CAMTA1 gene. Thevenon et al. reported three families with intragenic CAMTA1 rearrangements. The clinical and molecular findings of those families are presented in Supplementary Table 1. An additional patient with ID and autism who had a 94 Kb deletion in the CAMTA1 gene was also reported. Two of three patients from pedigree 1 reported by Thevenon et al had low information processing speed, slow memory consolidation, phonological disorders, and working memory deficits. All three patients had bilateral parietal and medial temporal abnormalities on brain magnetic resonance imaging (MRI) and PET images identified diffuse parieto-occipital and local left temporo-parietal decrease of 18-F-Fluoro-Desoxy-Glucose

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