Abstract
Autism spectrum disorders (ASD) are strikingly more prevalent in males, but the molecular mechanisms responsible for ASD sex-differential risk are poorly understood. Abnormally shorter telomeres have been associated with autism. Examination of relative telomere lengths (RTL) among non-syndromic male (N = 14) and female (N = 10) children with autism revealed that only autistic male children had significantly shorter RTL than typically-developing controls (N = 24) and paired siblings (N = 10). While average RTL of autistic girls did not differ significantly from controls, it was substantially longer than autistic boys. Our findings indicate a sexually-dimorphic pattern of RTL in childhood autism and could have important implications for RTL as a potential biomarker and the role/s of telomeres in the molecular mechanisms responsible for ASD sex-biased prevalence and etiology.
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Abbreviations
- ASD:
-
Autism spectrum disorders
- ADI-R:
-
Autism diagnostic interview-revised
- ANOVA:
-
Analysis of variance
- CV:
-
Coefficient of variation
- DSM-IV-TR:
-
Diagnostic and statistical manual of mental disorders, fourth edition, text revision
- ICD-10:
-
International statistical classification of diseases and related health problems version 10
- MMQPCR:
-
Monochrome multiplex quantitative PCR (qPCR)
- RTL:
-
Relative telomere length
- TERRA:
-
Telomeric repeat-containing RNA
- TL:
-
Telomere length
- TPE:
-
Telomere position effect
- T/S ratio:
-
Relative telomere to single-copy gene ratio
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Acknowledgments
We would like to thank Zahra Ghasemi, Mandana HadiJafari, Karim Dadashi Noshahr, and Elham Rostami for their help in the recruitment of the patients, sample collection, identification of the locally-matched healthy controls, and independent ADI-R. We would like to thank Joseph A. Baur, Ph.D. (Dept. of Physiology, University of Pennsylvania), F. Bradley Johnson, MD, Ph.D. (Dept. of Pathology and Laboratory Medicine, University of Pennsylvania), and John P. Murnane, Ph.D. (Dept. of Radiation Oncology, University of California, San Francisco) for careful reading of an earlier version of this manuscript and providing valuable comments. We are also thankful to Mohammad H. Rahbar, Ph.D. (Dept. of Internal Medicine, UT Health Science Center at Houston) for his helpful comments and suggestions during the 2015 IMFAR meeting in Shanghai, China.
Funding
This work was supported by Zanjan University of Medical Sciences (ZUMS) Grant Numbers A-12-534/1-4 and A-12-534/6-8.
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MP had the initial concept and supervised the project. MP and YP designed the study. YP set up and carried out the MMQPCR experiments. MRE, RSB, and MVF were involved in the initial recruitment of the autistic children, and they also took care of the clinical examination of the patients, diagnosis, and clinical follow-ups. MRE was in charge of the initial round of ADI-R. FSM and KhB were involved in the second round of independent ADI-R, saliva sample collection, and identification of candidate control subjects, and they also took care of gDNA extractions. ME was in charge of comparing and matching independent ADI-R scores and analysis. HP was involved in the statistical analysis of the data. YP and MP analyzed the data. YP provided the initial draft of the manuscript by getting feedback from team members. MP wrote and revised the full manuscript for submission. All authors read and approved the final manuscript.
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Panahi, Y., Salasar Moghaddam, F., Babaei, K. et al. Sexual Dimorphism in Telomere Length in Childhood Autism. J Autism Dev Disord 53, 2050–2061 (2023). https://doi.org/10.1007/s10803-022-05486-2
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DOI: https://doi.org/10.1007/s10803-022-05486-2