34. Angelman syndrome (AS) and Prader-Willi Syndrome (PWS) have very distinct symptoms. Factors responsible for the occurrence of these syndromes are given below:
A. Microdeletion of 15q 11-13 in paternal chromosome.
B. Uniparental disomy of maternal chromosome 15.
C. Lack of functional maternal copy of ubiquitin ligase E3A.
D. Lack of SNURF.SNRPN transcript, which is produced only from paternal chromosome.
E. Deficiencies of small nucleolar RNAs, which are encoded from the introns of SNURF-SNRPN transcript from paternal chromosome.
Which of the following combination of answers is correct for Angelman and Prader-Willi Syndromes
(1) PWS – A, C, D; AS – B, E
(2) PWS – B only; AS – A, C, D, E
(3) PWS – A, B, D, E; AS – C only
(4) PWS-A, B; AS-C, D, E

Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are distinct genetic disorders caused by abnormalities in the same region of chromosome 15 (15q11-13), but on different parental alleles due to genomic imprinting. The correct combination of answers describing the causes of these syndromes is: PWS involves factors A, B, D, and E, while AS involves factor C only.

Explanation of options:

A. Microdeletion of 15q11-13 in the paternal chromosome causes Prader-Willi syndrome. This deletion leads to loss of expression of paternally inherited genes in this region, which is critical in PWS pathogenesis.

B. Uniparental disomy (UPD) of maternal chromosome 15 means both copies of chromosome 15 are inherited from the mother. This also causes PWS because the paternal genes are missing or not expressed.

C. Lack of a functional maternal copy of ubiquitin ligase E3A (UBE3A) causes Angelman syndrome. UBE3A is imprinted, and only the maternal copy is active in certain brain areas, so its loss leads to AS symptoms.

D. Lack of SNURF-SNRPN transcript, produced only from the paternal chromosome, is involved in PWS. This transcript’s absence means paternal genes are not expressed.

E. Deficiencies of small nucleolar RNAs (snoRNAs), which are encoded in introns of the paternal SNURF-SNRPN transcript, contribute to Prader-Willi syndrome by disrupting normal gene expression.

Thus,

• Prader-Willi syndrome (PWS) is caused by A (paternal microdeletion), B (maternal uniparental disomy), D (lack of SNURF-SNRPN transcript), and E (deficiency of snoRNAs from paternal chromosome)

• Angelman syndrome (AS) is caused by C (loss of maternal UBE3A function).

The correct answer is option (3): PWS – A, B, D, E; AS – C only.

Introduction:
Angelman syndrome (AS) and Prader-Willi syndrome (PWS) are two distinct neurodevelopmental disorders caused by defects in the same chromosome 15q11-13 region, but result from abnormalities on different parental chromosomes due to genomic imprinting. Understanding their genetic causes is essential to diagnose and differentiate these syndromes, which have very different clinical symptoms.

Detailed Explanation of Genetic Causes:

• Prader-Willi Syndrome (PWS):
  PWS results from loss of expression of paternally inherited genes on chromosome 15q11-13. This occurs mainly due to microdeletions in the paternal chromosome (Option A), maternal uniparental disomy where both chromosome 15 copies come from the mother (Option B), or imprinting defects that silence paternal genes. Key transcripts missing include the SNURF-SNRPN transcript (Option D) and small nucleolar RNAs (Option E) encoded within SNURF-SNRPN introns. These gene losses disrupt normal hypothalamic function leading to characteristic symptoms such as hypotonia, hyperphagia, and developmental delays.

• Angelman Syndrome (AS):
  AS is caused primarily by loss of function of the ubiquitin ligase E3A gene (UBE3A) on the maternal chromosome 15 (Option C). In certain brain regions, only the maternal UBE3A allele is active, so its deletion or mutation leads to AS features including severe intellectual disability, speech impairment, motor difficulties, and a happy demeanor. Unlike PWS, AS is not caused by paternal deletions or snoRNA deficiencies.

This genetic mechanism of imprinting explains why deletions or abnormalities on the same chromosomal region can result in two clinically different syndromes depending on the parent of origin.

Selection of option (3) properly reflects the molecular and genetic basis of these imprinting disorders.

This explanation can supplement teaching and study materials for genetics and molecular biology, especially in understanding imprinting disorders and their diagnostic criteria.