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Continuous reference intervals for leukocyte telomere length in children: the method matters.

Analia Lesmana1, Pei Tian1, Vasiliki Karlaftis1,2

  • 1Murdoch Children's Research Institute, Parkville, Australia.

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|March 12, 2021
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Summary

Establishing age-matched reference intervals for telomere length (TL) in children is crucial for diagnosing conditions like bone marrow failure. This study provides method-specific continuous RIs for TL in children, aiding in accurate diagnosis and treatment.

Keywords:
hematopoiesismethodspediatricreference intervalstelomere length

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Area of Science:

  • Pediatric Hematology
  • Molecular Biology
  • Genetics

Background:

  • Very short telomeres in children are linked to severe conditions like bone marrow failure.
  • Accurate diagnosis of short telomeres requires age-matched reference intervals (RIs).
  • Identifying children with short telomeres can improve bone marrow transplantation outcomes.

Purpose of the Study:

  • To establish age-matched reference intervals (RIs) for telomere length (TL) in children.
  • To compare three common methods for measuring leukocyte telomere length in pediatric populations.
  • To provide method-specific continuous RIs for pediatric telomere length assessment.

Main Methods:

  • Recruited 212 healthy children aged 30 days to 18 years.
  • Measured leukocyte telomere length (TL) using terminal restriction fragment (TRF) analysis, quantitative PCR (QPCR), and Flow-FISH.
  • Utilized fractional polynomial models and quantile regression to generate continuous RIs, examining factors like age and gender.

Main Results:

  • Continuous RIs for TL were established as functions of age for each method.
  • TRF analysis and QPCR showed a significant negative correlation between TL and age (p<0.001).
  • Flow-FISH indicated no significant change in TL with age (p=0.23); gender did not influence TL.

Conclusions:

  • The study offers three distinct, method-specific continuous RIs for assessing pediatric telomere length.
  • The choice of method depends on sample availability, type, and desired sensitivity to age-related changes.
  • These RIs facilitate accurate diagnosis and monitoring of pediatric conditions associated with telomere length.