Interstitial 22q13 deletions: genes other than SHANK3 have major effects on cognitive and language development.
The severe mental retardation and speech deficits associated with 22q13 terminal deletions have been attributed in large part to haploinsufficiency of SHANK3, which maps to all 22q13 terminal deletions, although more proximal genes are assumed to have minor effects. We report two children with interstitial deletions of 22q13 and two copies of SHANK3, but clinical features similar to the terminal 22q13 deletion syndrome, including mental retardation and severe speech delay. Both these interstitial deletions are completely contained within the largest terminal deletion, but do not overlap with the nine smallest terminal deletions. These interstitial deletions indicate that haploinsufficiency for 22q13 genes other than SHANK3 can have major effects on cognitive and language development. However, the relatively mild speech problems and normal cognitive abilities of a parent who transmitted her identical interstitial deletion to her more severely affected son suggests that the phenotype associated with this region may be more variable than terminal deletions and therefore contribute to the relative lack of correlation between clinical severity and size of terminal deletions. The phenotypic similarity between the interstitial deletions and non-overlapping small terminal 22q13 deletions emphasizes the general nonspecificity of the clinical picture of the 22q13 deletion syndrome and the importance of molecular analysis for diagnosis.
Wilson
Heather L
HL
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
Crolla
John A
JA
Walker
Dena
D
Artifoni
Lina
L
Dallapiccola
Bruno
B
Takano
Takako
T
Vasudevan
Pradeep
P
Huang
Shuwen
S
Maloney
Vivienne
V
Yobb
Twila
T
Quarrell
Oliver
O
McDermid
Heather E
HE
D002352:Carrier Proteins; D002648:Child; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D007805:Language Development Disorders / Q000235:genetics* / Q000473:pathology; D008297:Male; D009419:Nerve Tissue Proteins; D013577:Syndrome
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; C492357:SHANK3 protein, human