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Clinical‐etiologic correlation in children with Prader‐Willi syndrome (PWS): An interdisciplinary study
Author(s) -
Torrado Maria,
Araoz Veronica,
Baialardo Edgardo,
Abraldes Karina,
Mazza Carmen,
Krochik Gabriela,
Ozuna Blanca,
Leske Vivian,
Caino Silvia,
Fano Virginia,
Chertkoff Lilien
Publication year - 2006
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31520
Subject(s) - imprinting (psychology) , uniparental disomy , hypopigmentation , biology , phenotype , genetics , correlation , genomic imprinting , genotype , physiology , chromosome , gene , dna methylation , karyotype , gene expression , geometry , mathematics
Prader‐Willi syndrome (PWS) is a multisystemic disorder caused by the loss of expression of paternally transcribed genes within chromosome 15q11‐q13. Most cases are due to paternal deletion of this region; the remaining cases result from maternal uniparental disomy (UPD) and imprinting defects. To better understand the phenotypic variability of PWS, a genotype–phenotype correlation study was performed in 91 children with PWS. Patients were diagnosed by Southern Blot Methylation assay and genetic subtypes were established using FISH and microsatellite analyses. Fifty‐nine subjects with deletion (31/28 males/females; mean age 3.86 years), 30 with UPD (14/16 males/females; mean age 3.89 years) and 2 girls with a presumed imprinting defect (mean age 0.43 yrs) were identified. For correlation purposes patients were grouped as “deleted” and “non‐deleted.” An increased maternal age was found in the UPD group. Four of Holm's criteria were more frequently present in the deleted group: need for special feeding techniques, sleep disturbance, hypopigmentation, and speech articulation defects. Concerning cognitive assessments, only 9.52% of subjects with deletion had Full‐Scale IQ (FSIQ) ≥70, while 61.53% of subjects without deletion had FSIQ ≥70. Similar results were found in behavioral measures. Sleep disorders and carbohydrate metabolism were systematically assessed. Polysomnoghaphic studies revealed a higher frequency of central events with desaturations ≥10% in the deleted group ( P = 0.020). In summary, the phenotype was significantly different between both groups in certain parameters related to the CNS. These results might be related to the differences in brain gene expression of the genetic subtypes. © 2006 Wiley‐Liss, Inc.