Summary
We previously proposed a phenotype-karyotype correlation in the Prader-Willi syndrome (PWS). In order to confirm this hypothesis, we analyzed the genomic DNA of 10 clinically typical PWS patients with various chromosome 15 abnormalities, consisting of four [del(15)(q11.1;q12)], one [del(15)(q11;q13)], one [−15,+der(15)(pter::?HSR::p11→q11.1::q12)], one [mos 45,X,del.(15)(q11.1;q12)/46,X,del(15)(q11.1;q12), +mar], two [t(15;15)(p11.2;q12)] and one [del(15)(q11.1;q12),+inv, dup(15)(q11.1;q11.1)], and that of one atypical PWS patient with an apparently normal karyotype. Densitometric analyses on autoradiographic bands of Southern hybridization using two DNA segments, pML34 and pTD3-21, as probes revealed that all 7 patients with an interstitial deletion of 15q11.2 or 15q11.2-12 band had only one copy for each of the probes. In the two patients with an unbalanced translocation 15q;15q, two copies of each sequence were retained in spite of a visible deletion of band 15q11. This suggests that both of the two sequences may localize in flank of a critical region for the PWS phenotype. The copy number for the two probes was two in the case with the data in otherde novo non-Robertsonian structural rearrangements (Chamberlin and Magenis, 1980).
A few PWS patients are familial (Hasegawaet al., 1984; Lubinskyet al., 1987; Cassidy, 1987). Prenatal diagnosis in a pregnancy following the birth of a PWS child have been performed cytogenetically (Emanuelet al., 1983; Smith, 1986), but no recurrence has been found in the pregnancies studied (Schinzel, 1986). It is often difficult to obtain convincing prometaphase chromosomes from culture amniotic cells. Thus, molecular-genetic analysis may be useful for prenatal, diagnosis, especially in familial cases. Neonatal diagnosis of PWS is more important clinically to prevent patients early from obesity and its subsequent diabetes. However, the clinical diagnosis in early infancy, is often difficult, because the time of onset of obesity is usually in around, childhood. Although neonatal diagnosis of PWS by chromosome analysis was recently succeeded (Greenberget al., 1987), a molecular genetic analysis as described here is also applicable to the diagnosis of presumed newborn patients, especially of patients with a normal karyotype.
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Kamei, T., Hamabe, Ji., Matsumoto, T. et al. A molecular deletion study with southern hybridization on typical Prader-Willi syndrome (PWS) patients with various chromosome abnormalities involving 15q11–12 and on an atypical PWS patient with apparently normal karyotype. Jap J Human Genet 33, 477–486 (1988). https://doi.org/10.1007/BF01897789
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DOI: https://doi.org/10.1007/BF01897789