Characteristics of two cases with dup(15) (q 11.2-q 12): one of maternal and one of paternal origin

Abstract

Purpose:The phenotype correlations for interstitial duplications that include the Prader-Willi/Angelman syndrome critical region are not well established. We describe two such duplication cases, one of which was of maternal origin and the other was paternal. Methods: High resolution G-banding, fluorescence in situ hybridization (FISH) for SNRP-N and D15S10 were used for cytogenetic analysis. Southern blot analyses based on parent of origin specific DNA methylation at D15S63 (PW71) locus were utilized for detection of methylated and unmethylated fragments. Results: The duplication was established by the FISH analysis. The molecular pattern suggested a maternal origin of the duplication in patient 1 and a paternal origin in patient 2. Patient 1 (2 years old) had developmental and speech delays with pervasive developmental disorder or mild autism, strabismus, and normal growth parameters with seizures. Patient 2 (16 years old) had global developmental delay, verbal IQ of 94, depression, obesity, food-seeking behavior, and significant behavioral problems that included self-injurious tendencies. Neither patient had significant dysmorphic features or abnormalities of internal organs. Conclusion: The two cases suggest that some patients with 15q11.2q12 duplication may have significant anomalies, and there appear to be phenotypic differences between maternal and paternal transmission of the duplication.

Array-based comparative genomic hybridization analysis of 1176 consecutive clinical genetics investigations

“…Excluding subtelomere regions, 11 abnormal cases had duplications in regions associated with known microdeletion syndromes. Because the reciprocal duplication of a typically microdeleted region may have a different or milder phenotypic effect, 12,13 focused FISH analysis may not be requested in the preliminary investigations, and thus, may remain undetected. aCGH studies allow for concurrent interro-gation all commonly microdeleted regions and identifies deletion and duplication, thus increasing the initial diagnostic yield.…”

A genomic point-of-view on environmental factors influencing the human brain methylome

“…For instance, while maternal duplication of 15q11-q13 (15q dup or idic15) is associated with autism in 85% of cases, 38 paternal 15q11-q13 duplication has been observed in healthy unaffected individuals 39 as well as cases with autism or language and social defects. [40][41][42][43][44] Therefore, a simple genotype-phenotype correlation with CNVs and neurodevelopmental disorders is not apparent.…”

Molecular Diagnosis of Prader–Willi and Angelman Syndromes by Methylation-Specific Melting Analysis and Methylation-Specific Multiplex Ligation-Dependent Probe Amplification

“…In addition to deletion and UPD, duplications of chromosome 15 q11-q12 have been described previously in patients with PWS-like or AS-like symptoms (25 ). To evaluate the possibility of using MS-MLPA to diagnose this rare duplication, we analyzed a cell line obtained from Coriell Repository (GM12135).…”