Question 1

What is the Meaning of H19/IGF2 Locus?

Accepted Answer

The H19/IGF2 locus, on human chromosome 11, houses H19 and IGF2 genes, exhibiting parent-of-origin specific expression. This genomic imprinting means their activity depends on parental inheritance. H19 encodes a long non-coding RNA, expressed maternally. IGF2 produces insulin-like growth factor 2, expressed paternally.

Question 2

What is the Context of H19/IGF2 Locus?

Accepted Answer

This locus functions within the complex regulatory network governing mammalian growth and development, critical for fetal and postnatal growth. Located at 11p15.5, it exemplifies epigenetic regulation in human physiology. Its proper function is essential for cell proliferation and differentiation, directly influencing organismal size and tissue development.

Question 3

What is the Significance of H19/IGF2 Locus?

Accepted Answer

Clinically, dysregulation within the H19/IGF2 locus links directly to human growth disorders, including Beckwith-Wiedemann Syndrome (BWS) and Silver-Russell Syndrome (SRS). Aberrations here cause overgrowth or growth restriction, impacting patient physical development and metabolic health. Understanding its status is vital for accurate diagnosis and management.

Question 4

What is the Mechanism of H19/IGF2 Locus?

Accepted Answer

H19 and IGF2 expression is reciprocally regulated by an Imprinting Control Region (ICR) upstream of H19. On the maternal chromosome, the unmethylated ICR permits H19 expression, insulating and blocking IGF2 activation. On the paternal chromosome, the ICR is methylated, silencing H19 and allowing IGF2 transcription. This precise epigenetic switch ensures balanced growth.

Question 5

What is the Application of H19/IGF2 Locus?

Accepted Answer

In clinical practice, molecular genetic testing of the H19/IGF2 locus is a diagnostic tool for individuals presenting with features suggesting BWS or SRS. Analysis of methylation patterns and gene dosages at this region confirms diagnosis, guiding subsequent medical surveillance and intervention. This application aids in tailoring patient care based on genetic profile.

Question 6

What is the Metric of H19/IGF2 Locus?

Accepted Answer

Assessment of the H19/IGF2 locus typically involves specialized molecular diagnostic techniques. These include methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) or bisulfite sequencing, which quantitatively measure the methylation status of the Imprinting Control Region. Genetic sequencing can also identify point mutations or deletions within the genes, providing comprehensive insight.

Question 7

What is the Risk of H19/IGF2 Locus?

Accepted Answer

Misregulation or genetic alterations within the H19/IGF2 locus carry clinical risks. Aberrant methylation or chromosomal rearrangements can lead to characteristic BWS features, including macroglossia, omphalocele, and increased embryonal tumor predisposition. Conversely, paternal allele hypomethylation causes SRS, characterized by severe pre- and postnatal growth restriction and relative macrocephaly. Vigilant medical oversight is essential.

H19/IGF2 Locus

Meaning

Context

Significance

Mechanism

Application

Metric

Risk

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