TY - JOUR
T1 - Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects
AU - Zhao, Yingjie
AU - Guo, Tingwei
AU - Fiksinski, Ania
AU - Breetvelt, Elemi
AU - McDonald-McGinn, Donna M.
AU - Crowley, Terrence B.
AU - Diacou, Alexander
AU - Schneider, Maude
AU - Eliez, Stephan
AU - Swillen, Ann
AU - Breckpot, Jeroen
AU - Vermeesch, Joris
AU - Chow, Eva W. C.
AU - Gothelf, Doron
AU - Duijff, Sasja
AU - Evers, Rens
AU - van Amelsvoort, Therese A.
AU - van den Bree, Marianne
AU - Owen, Michael
AU - Niarchou, Maria
AU - Bearden, Carrie E.
AU - Ornstein, Claudia
AU - Pontillo, Maria
AU - Buzzanca, Antonino
AU - Vicari, Stefano
AU - Armando, Marco
AU - Murphy, Kieran C.
AU - Murphy, Clodagh
AU - Garcia-Minaur, Sixto
AU - Philip, Nicole
AU - Campbell, Linda
AU - Morey-Canellas, Jaume
AU - Raventos, Jasna
AU - Rosell, Jordi
AU - Heine-Suner, Damian
AU - Shprintzen, Robert J.
AU - Gur, Raquel E.
AU - Zackai, Elaine
AU - Emanuel, Beverly S.
AU - Wang, Tao
AU - Kates, Wendy R.
AU - Bassett, Anne S.
AU - Vorstman, Jacob A. S.
AU - Morrow, Bernice E.
AU - Int Brain Behavior Consortium
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
KW - 22q11.2 deletion syndrome
KW - deletion size
KW - intellectual disability
KW - IQ
KW - low copy repeat
KW - segmental duplication
KW - CARDIO-FACIAL-SYNDROME
KW - CONGENITAL HEART-DISEASE
KW - SCHOOL-AGED CHILDREN
KW - VELOCARDIOFACIAL SYNDROME
KW - NEURODEVELOPMENTAL OUTCOMES
KW - DEVELOPMENTAL TRAJECTORIES
KW - COGNITIVE DECLINE
KW - FOLLOW-UP
KW - BRAIN
KW - INTELLIGENCE
U2 - 10.1002/ajmg.a.40359
DO - 10.1002/ajmg.a.40359
M3 - Article
C2 - 30289625
SN - 1552-4825
VL - 176
SP - 2172
EP - 2181
JO - American Journal of Medical Genetics Part A
JF - American Journal of Medical Genetics Part A
IS - 10
ER -