Download PDF
CC BY 4.0 · Glob Med Genet 2022; 09(01): 018-022
DOI: 10.1055/s-0041-1736236
Original Article

Genetic Analysis of Neuroligin 4Y Gene in Autism Population of India

Rajat Hegde
1   Laboratory of Vascular Physiology and Medicine, Department of Physiology, Shri B.M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, Karnataka, India
2   Karnataka Institute for DNA Research, Dharwad, Karnataka, India
,
Smita Hegde
2   Karnataka Institute for DNA Research, Dharwad, Karnataka, India
3   Human Genetics Laboratory, Department of Anatomy, Shri B.M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, Karnataka, India
,
Suyamindra S. Kulkarni
2   Karnataka Institute for DNA Research, Dharwad, Karnataka, India
,
Aditya Pandurangi
4   Department of Psychiatry, Dharwad Institute of Mental Health and Neurosciences, Dharwad, Karnataka, India
,
Pramod B. Gai
2   Karnataka Institute for DNA Research, Dharwad, Karnataka, India
,
Kusal K. Das
1   Laboratory of Vascular Physiology and Medicine, Department of Physiology, Shri B.M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, Karnataka, India
› Author Affiliations Funding This study was supported by Grant-in-Aid for research from Department of Higher Education, Govt. of Karnataka, India (grant no: ED 15 UKV 2018).
› Further Information
   Permissions and Reprints

Abstract

Background Autism is one of the most complex, heterogeneous neurological disorders. It is characterized mainly by abnormal communication, impaired social interaction, and restricted behaviors. Prevalence of autism is not clear in Indian population.

Aim The present study hypothesized that Y chromosome plays role in sex bias of autism in Indian autistic population. To investigate our hypothesis, we underwent genetic analysis of neuroligin 4Y [NLGN4Y] gene by sequencing 85 male autistic children after screening large population of 1,870 mentally ill children from North Karnataka region of India.

Result Detailed sequencing of the single targeted gene revealed nine variants including, one novel missense mutation and eight synonymous variants; this accounts for 88.9% of synonymous variants. A single novel missense mutation is predicted to be nonpathogenic on the functions of neuroligin4Y protein but it slightly affects the local configuration by altering the original structure of a protein by changing charge and size of amino acid.

Conclusion Probably NLGN4Y gene may not be the risk factor for autism in male children in Indian autistic population. Functional analysis was an important limitation of our study. Therefore, detailed functional analysis is necessary to determine the exact role of novel missense mutation of neuroligin 4Y [NLGN4Y] gene especially in the male predominance of autism in Indian autistic population.

Keywords

autism - neuroligin 4Y - India - novel missense mutation - male predominance

Ethical Approval

Ethical approval for the study was taken from Institutional Ethical Committee of Shri B.M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapura, [Ref No: BLDE (DU) IEC/337–2018–19]. Informed written consent was obtained from parents/guardians before the collection of blood samples.




Publication History

Received: 30 June 2021

Accepted: 16 August 2021

Article published online:
28 September 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Spence SJ. The genetics of autism. Semin Pediatr Neurol 2004; 11 (03) 196-204
    CrossrefPubMedGoogle Scholar
  • 2 Nguyen TA, Lehr AW, Roche KW. Neuroligins and neurodevelopmental disorders: X-linked genetics. Front Synaptic Neurosci 2020; 12: 33
    CrossrefPubMedGoogle Scholar
  • 3 Boucard AA, Chubykin AA, Comoletti D, Taylor P, Südhof TC. A splice code for trans-synaptic cell adhesion mediated by binding of neuroligin 1 to α- and β-neurexins. Neuron 2005; 48 (02) 229-236
    CrossrefPubMedGoogle Scholar
  • 4 Nguyen TA, Wu K, Pandey S. et al. A cluster of autism-associated variants on X-linked NLGN4X functionally resemble NLGN4Y. Neuron 2020; 106 (05) 759-768.e7
    CrossrefPubMedGoogle Scholar
  • 5 Bemben MA, Shipman SL, Nicoll RA, Roche KW. The cellular and molecular landscape of neuroligins. Trends Neurosci 2015; 38 (08) 496-505
    CrossrefPubMedGoogle Scholar
  • 6 Jeong J, Paskus JD, Roche KW. Posttranslational modifications of neuroligins regulate neuronal and glial signaling. Curr Opin Neurobiol 2017; 45: 130-138
    CrossrefPubMedGoogle Scholar
  • 7 Ross JL, Bloy L, Roberts TPL. et al. Y chromosome gene copy number and lack of autism phenotype in a male with an isodicentric Y chromosome and absent NLGN4Y expression. Am J Med Genet B Neuropsychiatr Genet 2019; 180 (07) 471-482
    CrossrefPubMedGoogle Scholar
  • 8 Venselaar H, Te Beek TAH, Kuipers RKP, Hekkelman ML, Vriend G. Protein structure analysis of mutations causing inheritable diseases. An e-Science approach with life scientist friendly interfaces. BMC Bioinformatics 2010; 11 (01) 548
    CrossrefPubMedGoogle Scholar
  • 9 Kanner L. Follow-up study of eleven autistic children originally reported in 1943. J Autism Child Schizophr 1971; 1 (02) 119-145
    CrossrefPubMedGoogle Scholar
  • 10 Lawson-Yuen A, Saldivar JS, Sommer S, Picker J. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur J Hum Genet 2008; 16 (05) 614-618
    CrossrefPubMedGoogle Scholar
  • 11 Yan J, Oliveira G, Coutinho A. et al. Analysis of the neuroligin 3 and 4 genes in autism and other neuropsychiatric patients. Mol Psychiatry 2005; 10 (04) 329-332
    CrossrefPubMedGoogle Scholar
  • 12 Kent R, Simonoff E. Prevalence of Anxiety in Autism Spectrum Disorders. Anxiety in Children and Adolescents with Autism Spectrum Disorder: Evidence-Based Assessment and Treatment. Elsevier Inc.; Academic Press; United States: 2017: 5-32
    CrossrefGoogle Scholar
  • 13 Volaki K, Pampanos A, Kitsiou-Tzeli S. et al. Mutation screening in the Greek population and evaluation of NLGN3 and NLGN4X genes causal factors for autism. Psychiatr Genet 2013; 23 (05) 198-203
    CrossrefPubMedGoogle Scholar
  • 14 Ross JL, Tartaglia N, Merry DE, Dalva M, Zinn AR. Behavioral phenotypes in males with XYY and possible role of increased NLGN4Y expression in autism features. Genes Brain Behav 2015; 14 (02) 137-144
    CrossrefPubMedGoogle Scholar
  • 15 Ylisaukko-oja T, Rehnström K, Auranen M. et al. Analysis of four neuroligin genes as candidates for autism. Eur J Hum Genet 2005; 13 (12) 1285-1292
    CrossrefPubMedGoogle Scholar
  • 16 Sand P, Langguth B, Hajak G. et al. Screening for neuroligin 4 (NLGN4) truncating and transmembrane domain mutations in schizophrenia. Schizophr Res 2006; 82 (2-3): 277-278
    CrossrefPubMedGoogle Scholar
  • 17 Serajee FJ, Mahbubul Huq AH. Association of Y chromosome haplotypes with autism. J Child Neurol 2009; 24 (10) 1258-1261
    CrossrefPubMedGoogle Scholar
  • 18 Yan J, Feng J, Schroer R. et al. Analysis of the neuroligin 4Y gene in patients with autism. Psychiatr Genet 2008; 18 (04) 204-207
    CrossrefPubMedGoogle Scholar