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Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects.

ABSTRACT: The 22q11.2 deletion syndrome is caused by non-allelic homologous recombination events during meiosis between low copy repeats (LCR22) termed A, B, C, and D. Most patients have a typical LCR22A-D (AD) deletion of 3 million base pairs (Mb). In this report, we evaluated IQ scores in 1,478 subjects with 22q11.2DS. The mean of full scale IQ, verbal IQ, and performance IQ scores in our cohort were 72.41 (standard deviation-SD of 13.72), 75.91(SD of 14.46), and 73.01(SD of 13.71), respectively. To investigate whether IQ scores are associated with deletion size, we examined individuals with the 3 Mb, AD (n = 1,353) and nested 1.5 Mb, AB (n = 74) deletions, since they comprised the largest subgroups. We found that full scale IQ was decreased by 6.25 points (p = .002), verbal IQ was decreased by 8.17 points (p = .0002) and performance IQ was decreased by 4.03 points (p = .028) in subjects with the AD versus AB deletion. Thus, individuals with the smaller, 1.5 Mb AB deletion have modestly higher IQ scores than those with the larger, 3 Mb AD deletion. Overall, the deletion of genes in the AB region largely explains the observed low IQ in the 22q11.2DS population. However, our results also indicate that haploinsufficiency of genes in the LCR22B-D region (BD) exert an additional negative impact on IQ. Furthermore, we did not find evidence of a confounding effect of severe congenital heart disease on IQ scores in our cohort.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC6209529 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects.

Zhao Yingjie Y Guo Tingwei T Fiksinski Ania A Breetvelt Elemi E McDonald-McGinn Donna M DM Crowley Terrence B TB Diacou Alexander A Schneider Maude M Eliez Stephan S Swillen Ann A Breckpot Jeroen J Vermeesch Joris J Chow Eva W C EWC Gothelf Doron D Duijff Sasja S Evers Rens R van Amelsvoort Thérèse A TA van den Bree Marianne M Owen Michael M Niarchou Maria M Bearden Carrie E CE Ornstein Claudia C Pontillo Maria M Buzzanca Antonino A Vicari Stefano S Armando Marco M Murphy Kieran C KC Murphy Clodagh C Garcia-Minaur Sixto S Philip Nicole N Campbell Linda L Morey-Cañellas Jaume J Raventos Jasna J Rosell Jordi J Heine-Suner Damian D Shprintzen Robert J RJ Gur Raquel E RE Zackai Elaine E Emanuel Beverly S BS Wang Tao T Kates Wendy R WR Bassett Anne S AS Vorstman Jacob A S JAS Morrow Bernice E BE

American journal of medical genetics. Part A 20181005 10

The 22q11.2 deletion syndrome is caused by non-allelic homologous recombination events during meiosis between low copy repeats (LCR22) termed A, B, C, and D. Most patients have a typical LCR22A-D (AD) deletion of 3 million base pairs (Mb). In this report, we evaluated IQ scores in 1,478 subjects with 22q11.2DS. The mean of full scale IQ, verbal IQ, and performance IQ scores in our cohort were 72.41 (standard deviation-SD of 13.72), 75.91(SD of 14.46), and 73.01(SD of 13.71), respectively. To inv ...[more]

PMID: 30289625

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Project description:22q11.2 deletion syndrome is characterised by a well defined microdeletion that is associated with a high risk of neuropsychiatric disorders, including intellectual disability, schizophrenia, attention-deficit hyperactivity disorder, autism spectrum disorder, anxiety disorders, seizures and epilepsy, and early-onset Parkinson's disease. Preclinical and clinical data reveal substantial variability of the neuropsychiatric phenotype despite the shared underlying deletion in this genetic model. Factors that might explain this variability include genetic background effects, additional rare pathogenic variants, and potential regulatory functions of some genes in the 22q11.2 deletion region. These factors might also be relevant to the pathophysiology of these neuropsychiatric disorders in the general population. We review studies that might provide insight into pathophysiological mechanisms underlying the expression of neuropsychiatric disorders in 22q11.2 deletion syndrome, and potential implications for these common disorders in the general (non-deleted) population. The recurrent hemizygous 22q11.2 deletion, associated with 22q11.2 deletion syndrome, has attracted attention as a genetic model for common neuropsychiatric disorders because of its association with substantially increased risk of such disorders.1 Studying such a model has many advantages. First, 22q11.2 deletion has been genetically well characterised.2 Second, most genes present in the region typically deleted at the 22q11.2 locus are expressed in the brain.3-5 Third, genetic diagnosis might be made early in life, long before recognisable neuropsychiatric disorders have emerged. Thus, this genetic condition offers a unique opportunity for early intervention, and monitoring individuals with 22q11.2 deletion syndrome throughout life could provide important information on factors contributing to disease risk and protection. Despite the commonly deleted region being shared by about 90% of individuals with 22q11.2 deletion syndrome, neuropsychiatric outcomes are highly variable between individuals and across the lifespan. A clear link remains to be established between genotype and phenotype.3,5 In this Review, we summarise preclinical and clinical studies investigating biological mechanisms in 22q11.2 deletion syndrome, with a focus on those that might provide insight into mechanisms underlying neuropsychiatric disorders in 22q11.2 deletion syndrome and in the general population.

Dataset Information

Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects.

Publications

Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects.

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