A de novo unbalanced reciprocal translocation identified as paternal in origin in the Prader-Willi syndrome

Abstract

Interstitial cytogenetic deletions involving the paternally derived chromosome 15q11-13 have been described in patients with the Prader-Willi syndrome (PWS). We report a child with PWS and a de novo unbalanced karyotype -45,XY,-9,-15,+der(9)t(9;15)(q34;q13). Molecular studies with the DNA probe pML34 confirmed that only a single Prader Willi critical region (PWCR:15q11.2-q12) copy was present. Hybridisation of patient and parental DNA with the multi-allelic probe CMW1, which maps to pter-15q13, showed that the chromosome involved in the translocation was paternal in origin. This is the first example of a paternally-derived PWCR allele loss caused by an unbalanced translocation that has arisen de novo.

The phenomenology and diagnosis of psychiatric illness in people with Prader–Willi syndrome

“…It was previously found that the inheritance of a familial balanced translocation is inherited in unbalanced form in the proband resulting in a 15q11–q13 deletion (Webb et al 1995). Furthermore, other reports have demonstrated that unbalanced translocations causing PWS can result in monosomy of the PWSCR (Smith et al 1991; Horsthemke et al 1996; Klein et al 2004) and therefore are effectively similar to deletions at this region. The genetic configurations of PWS caused by mUPD and PWS caused by an imprinting defect are also similar: in individuals with an imprinting defect, the imprinting centre fails to reset as paternal the imprint on the chromosome 15 homologue inherited from the father's mother, giving apparent maternal disomy, although non-imprinted genes from the father are still present (Buiting et al 1995).…”

Genotype-Phenotype Relationships and Endocrine Findings in Prader-Willi Syndrome

“…After methylation status confirmation, defining the exact molecular mechanism behind the syndrome origin is important for genetic counseling. Sporadic deletion cases have <1% risk of recurrence, while rare cases of structural abnormalities involving chromosome 15 (such as translocations, ring formation, isochromosome or inversions) can be as high as 25-50% and fluorescence in situ hybridization (FISH) can address the deletion source (59)(60)(61)(62)(63)(64)(65). mUPD 15 is typically de novo (recurrence <1%), proband and parents should be investigated by small nucleotide polymorphisms (SNP) microarray for accurate counseling (66,67).…”

The dilemma of diagnostic testing for Prader-Willi syndrome

“…These mechanisms can be arrived at by occurring de novo or as a result of a structural abnormality, such as a translocation, ring formation, isochromosome, or inversion, involving chromosomes 15 alone or with some other chromosome. A rearrangement occurs in ~5% of individuals with PWS (25). These structural rearrangements may be balanced or unbalanced, the commonest being Robertsonian translocations (14;15) and (15;15) (25)(26)(27)(28)(29)(30).…”

“…A rearrangement occurs in ~5% of individuals with PWS (25). These structural rearrangements may be balanced or unbalanced, the commonest being Robertsonian translocations (14;15) and (15;15) (25)(26)(27)(28)(29)(30).…”