Language and Neuropsychological Evaluations In Maternal Int Dup (15) Autism Cases

Background: It has been estimated that as many as ~3-5% of all autism cases may be the result of maternal duplications of the 15q11-q13 region. A key structural feature of chromosome 15 is the high number of low copy repeats (LCRs), which predispose to both deletion and duplication events mediated by non-allelic homologous recombination (NAHR). The 15q11-q13 region has a 2-Mb cluster domain of genes preferentially expressed from one parental allele referred to as the PWS/AS critical region. There are two main types of deletion/duplication: class I deletions/duplications with breakpoints at BP1 (proximal) to BP3 (distal) and class II deletions/duplications with breakpoints from BP2 (proximal) to BP3 (distal). There are 4 genes between BP1 and BP2

Objectives: The aim of the present study was to determine if individuals with maternal interstitial 15q duplications class I and II have phenotypic differences in language and neuropsychological evaluations.

Methods: ADOS/ADI-R were used for autism diagnosis. Peabody Picture vocabulary test four edition (PPVT-4) was done to evaluate receptive vocabulary. The neuropsychological tests done, were IQ and Vineland-II.

Results: Nine patients were recruited through the IDEAS parent support group (www.idic15.org): 4 class I and 3 class II were available for the analysis. All subjects scored as ASD upon ADOS/ADI-R analysis. In the neuropsychological evaluations 2/5 subjects had a low average IQ score, 3/5 were borderline. Most of the subjects had a low-moderate adaptive functioning score on the Vineland II evaluation with no differences among groups. All subjects performed below age corrected average for receptive vocabulary (PPVT-IV) but we found a significant difference (pval<0.03) between class I and class II subjects.

Conclusions: Language trends will require more subjects to be accurately described. Interestingly there are no major phenotypic differences in maternal deletion subjects (Angelman syndrome), except for the lack of verbal language in Class I patients, so it will be important to determine the roll in language of those four extra genes duplicated/deleted in Class I patients.