35. Which one of the following conditions associated with chromosome 15 may cause Prader-Willi syndrome?
(1) Paternal uniparental disomy
(2) Maternal uniparental disomy
(3) Imprinting of 15q11-q13 locus in maternal copy
(4) Imprinting of 15q23-q25 locus in paternal copy
Correct Answer: (2) Maternal uniparental disomy
Prader-Willi syndrome (PWS) arises from the loss of paternally expressed genes in the 15q11-q13 region of chromosome 15, due to mechanisms like paternal deletion (70% of cases), maternal uniparental disomy (UPD, 25-30% of cases), or imprinting defects (1-3%). In maternal UPD, both chromosome 15 copies come from the mother, silencing the needed paternal genes via genomic imprinting, which leads to PWS symptoms such as hypotonia, hyperphagia, and obesity.
Option Analysis
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(1) Paternal uniparental disomy: Both chromosome 15 copies from the father silence maternal genes (15q11-q13), causing Angelman syndrome, not PWS.
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(2) Maternal uniparental disomy: Correct; no paternal chromosome 15 means loss of paternally active genes at 15q11-q13, triggering PWS.
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(3) Imprinting of 15q11-q13 locus in maternal copy: Normal maternal imprinting silences these genes anyway; abnormal paternal imprinting causes PWS, while maternal defects link to Angelman.
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(4) Imprinting of 15q23-q25 locus in paternal copy: Incorrect locus; PWS involves 15q11-q13, not 15q23-q25.
Introduction
Prader-Willi syndrome chromosome 15 conditions, especially maternal uniparental disomy, disrupt genomic imprinting at 15q11-q13, leading to loss of paternal gene expression and symptoms like hypotonia and obesity. This key CSIR NET Life Sciences topic highlights how chromosome 15 inheritance errors cause PWS, contrasting with Angelman syndrome from paternal UPD.
