Novel Microduplication of CHL1 Gene in a Patient with Autism Spectrum Disorder: a Case Report and a Brief Literature Review

Overview

Journal Mol Cytogenet

Publisher Biomed Central

Specialty Biochemistry

Date 2016 Jun 30

PMID 27354858

Citations 17

Authors

Chunyang Li

Chunxue Liu

Bingrui Zhou

Chunchun Hu

Xiu Xu

Affiliations

Soon will be listed here.

Abstract

Background: The cell adhesion molecule L1-like (CHL1 or CALL) gene is located on chromosome 3p26.3, and it is highly expressed in the central and peripheral nervous systems. The protein encoded by this gene is a member of the L1 family of neural cell adhesion molecules, and it plays a role in nervous system development and synaptic plasticity. Moreover, studies of mice have revealed that CHL1 is a prime candidate gene for a dosage-sensitive autosomal form of mental retardation. To date, four patients with a microdeletion and two with a microduplication of 3p26.3 encompassing only the CHL1 gene have been reported in literature.

Case Presentation: In the present study, we have described a 16-month-old boy with autism spectrum disorder (ASD), developmental delay and minor dysmorphic facial features. This is the first report of a duplication of 3p26.3 including only the CHL1 gene in an ASD patient, and this duplication is the smallest reported to date in this gene. We also reviewed CHL1 gene mutation cases and examined whether this gene has an important role in cognitive function.

Conclusions: We conclude that both CHL1 deletions and duplications are likely responsible for the patient's impaired cognitive function, and CHL1 may be an intriguing ASD candidate gene.

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References

Hurley R, Losh M, Parlier M, Reznick J, Piven J . The broad autism phenotype questionnaire. J Autism Dev Disord. 2006; 37(9):1679-90. DOI: 10.1007/s10803-006-0299-3. View

Girirajan S, Eichler E . Phenotypic variability and genetic susceptibility to genomic disorders. Hum Mol Genet. 2010; 19(R2):R176-87. PMC: 2953748. DOI: 10.1093/hmg/ddq366. View

Demyanenko G, Siesser P, Wright A, Brennaman L, Bartsch U, Schachner M . L1 and CHL1 Cooperate in Thalamocortical Axon Targeting. Cereb Cortex. 2010; 21(2):401-12. PMC: 3020587. DOI: 10.1093/cercor/bhq115. View

Tassano E, Biancheri R, Denegri L, Porta S, Novara F, Zuffardi O . Heterozygous deletion of CHL1 gene: detailed array-CGH and clinical characterization of a new case and review of the literature. Eur J Med Genet. 2014; 57(11-12):626-9. DOI: 10.1016/j.ejmg.2014.09.007. View

Frints S, Marynen P, Hartmann D, Fryns J, Steyaert J, Schachner M . CALL interrupted in a patient with non-specific mental retardation: gene dosage-dependent alteration of murine brain development and behavior. Hum Mol Genet. 2003; 12(13):1463-74. DOI: 10.1093/hmg/ddg165. View

Bayou N, Mrad R, Ahlem B, Helayem M, Chaabouni H . Autism: an overview of genetic aetiology. Tunis Med. 2009; 86(6):573-8. View

Morag A, Pasmanik-Chor M, Oron-Karni V, Rehavi M, Stingl J, Gurwitz D . Genome-wide expression profiling of human lymphoblastoid cell lines identifies CHL1 as a putative SSRI antidepressant response biomarker. Pharmacogenomics. 2011; 12(2):171-84. DOI: 10.2217/pgs.10.185. View

Moghadasi S, van Haeringen A, Langendonck L, Gijsbers A, Ruivenkamp C . A terminal 3p26.3 deletion is not associated with dysmorphic features and intellectual disability in a four-generation family. Am J Med Genet A. 2014; 164A(11):2863-8. DOI: 10.1002/ajmg.a.36700. View

Conrad B, Antonarakis S . Gene duplication: a drive for phenotypic diversity and cause of human disease. Annu Rev Genomics Hum Genet. 2007; 8:17-35. DOI: 10.1146/annurev.genom.8.021307.110233. View

10.

Shuib S, McMullan D, Rattenberry E, Barber R, Rahman F, Zatyka M . Microarray based analysis of 3p25-p26 deletions (3p- syndrome). Am J Med Genet A. 2009; 149A(10):2099-105. DOI: 10.1002/ajmg.a.32824. View

11.

Yang C, Tan H, Du Y . The developmental disruptions of serotonin signaling may involved in autism during early brain development. Neuroscience. 2014; 267:1-10. DOI: 10.1016/j.neuroscience.2014.02.021. View

12.

Angeloni D, Lindor N, Pack S, Latif F, Wei M, Lerman M . CALL gene is haploinsufficient in a 3p- syndrome patient. Am J Med Genet. 1999; 86(5):482-5. DOI: 10.1002/(sici)1096-8628(19991029)86:5<482::aid-ajmg15>3.0.co;2-l. View

13.

Schmalbach B, Lepsveridze E, Djogo N, Papashvili G, Kuang F, Leshchynska I . Age-dependent loss of parvalbumin-expressing hippocampal interneurons in mice deficient in CHL1, a mental retardation and schizophrenia susceptibility gene. J Neurochem. 2015; 135(4):830-44. DOI: 10.1111/jnc.13284. View

14.

Cuoco C, Ronchetto P, Gimelli S, Bena F, Divizia M, Lerone M . Microarray based analysis of an inherited terminal 3p26.3 deletion, containing only the CHL1 gene, from a normal father to his two affected children. Orphanet J Rare Dis. 2011; 6:12. PMC: 3090742. DOI: 10.1186/1750-1172-6-12. View

15.

Te Weehi L, Maikoo R, Mc Cormack A, Mazzaschi R, Ashton F, Zhang L . Microduplication of 3p26.3 implicated in cognitive development. Case Rep Genet. 2014; 2014:295359. PMC: 3978399. DOI: 10.1155/2014/295359. View

16.

. Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR Surveill Summ. 2014; 63(2):1-21. View

17.

Pohjola P, de Leeuw N, Penttinen M, Kaariainen H . Terminal 3p deletions in two families--correlation between molecular karyotype and phenotype. Am J Med Genet A. 2010; 152A(2):441-6. DOI: 10.1002/ajmg.a.33215. View

18.

Kleene R, Chaudhary H, Karl N, Katic J, Kotarska A, Guitart K . Interaction between CHL1 and serotonin receptor 2c regulates signal transduction and behavior in mice. J Cell Sci. 2015; 128(24):4642-52. DOI: 10.1242/jcs.176941. View

19.

Salyakina D, Cukier H, Lee J, Sacharow S, Nations L, Ma D . Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk. PLoS One. 2011; 6(10):e26049. PMC: 3189231. DOI: 10.1371/journal.pone.0026049. View

20.

Toro R, Konyukh M, Delorme R, Leblond C, Chaste P, Fauchereau F . Key role for gene dosage and synaptic homeostasis in autism spectrum disorders. Trends Genet. 2010; 26(8):363-72. DOI: 10.1016/j.tig.2010.05.007. View