A variety of genetic mechanisms are associated with the Prader–Willi syndrome

Abstract

An extensive set of chromosome 15 DNA polymorphisms and densitometric analysis with four markers mapping to the Prader-Willi chromosome region (PWCR) of chromosome 15 have been used to characterize a cohort of 30 subjects with classical Prader-Willi syndrome (PWS). Molecular analysis enabled the classification of the PWS subjects into four groups: (A) 18 subjects (60%) had deletions of paternal 15q11-13 involving a common set of DNA markers. Two subjects had differently sized deletions, one larger and one smaller than the other cases. (B) Eight (27%) had maternal uniparental disomy for chromosome 15. (C) One (3%) had a marker chromosome carrying an extra copy of the PWCR. The marker chromosome was demonstrated to be of paternal origin and the two intact chromosomes were maternally derived. This case represents an apparent exception to the generally held view that PWS is associated with an absence of paternally inherited gene(s) located in the PWCR. (D) The remaining three cases (10%) had none of the above abnormalities. This last subgroup of patients has not previously been well characterized but could represent limited deletions not detectable with the markers used or abnormalities in the imprinting process. These cases represent potentially valuable resources to elucidate more precisely the fundamental disorders responsible for PWS.

Complex and segmental uniparental disomy updated

“…In the maternal heterodisomy group nine patients with a Robertsonian translocation were maternally inherited 22 24 25 28 118 – 120 124 125. PWS due to maternal UPD 15 was reported in three families with a maternal 14/15 translocation,34 35 128 and in two families with a maternal 13/15 translocation 32 33. So far, only one case of Angelman syndrome due to paternal UPD 15, associated with a Robertsonian translocation, has been described 124…”

“…In table 4 of the 2001 review (UPD of a part or of a whole chromosome directly involved in or associated with a complex structural and/or numeric chromosomal complement), only 13 cases with a supernumerary marker or ring chromosome were listed 35 69 77 78 80 – 85 88. Now, these cases and, to the best of my knowledge, 20 new cases136 – 153 are discussed separately (table 4).…”

Genetic Studies of Prader-Willi Patients Provide Evidence for Conservation of Genomic Architecture in Proximal Chromosome 15q

“…Similarly, mUPD has been shown to occur in approximately 25% of PWS patients in Western populations (Robinson et al, 1991;Mascari et al, 1992;Woodage et al, 1994). The inheritance of both copies of chromosome 15 from the mother results in the absence of expression of paternal genes at 15q11-q13 and, consequently, the PWS phenotype.…”

Very high birth weight of offspring is associated with an increased risk of leukemia in their mothers: Results of a population-based cohort study

“…Our finding of a specific association of leukemia in mothers of infants in the very high birth weight category rather than a continuous relation with increasing birthweight raises questions regarding specific macrosomic phenotypes and their relation to maternal leukemia. Beckwith-Wiedemann, and Prader Willi syndromes are disorders related to excessive growth, uniparental disomy and abnormal imprinting [28,29]; both syndromes have been associated with leukemia in affected individuals [30][31][32][33][34], but have not been reported with maternal cancer. We excluded parents of children with congenital anomalies, which have themselves been reported as risk factors for leukemia [35].…”