A De Novo Marker Chromosome Derived from 9p in a Patient with 9p Partial Duplication Syndrome and Autism Features: Genotype-phenotype Correlation

Overview

Journal BMC Med Genet

Publisher Biomed Central

Specialty Genetics

Date 2010 Sep 23

PMID 20858261

Citations 14

Authors

Khaled K Abu-Amero

Ali M Hellani

Mustafa A Salih

Mohammad Z Seidahmed

Tageldin S Elmalik

Ghassan Zidan

Thomas M Bosley

Affiliations

Soon will be listed here.

Abstract

Background: Previous studies focusing on candidate genes and chromosomal regions identified several copy number variations (CNVs) associated with increased risk of autism or autism spectrum disorders (ASD).

Case Presentation: We describe a 17-year-old girl with autism, severe mental retardation, epilepsy, and partial 9p duplication syndrome features in whom GTG-banded chromosome analysis revealed a female karyotype with a marker chromosome in 69% of analyzed metaphases. Array CGH analysis showed that the marker chromosome originated from 9p24.3 to 9p13.1 with a gain of 38.9 Mb. This mosaic 9p duplication was detected only in the proband and not in the parents, her four unaffected siblings, or 258 ethnic controls. Apart from the marker chromosome, no other copy number variations (CNVs) were detected in the patient or her family. Detailed analysis of the duplicated region revealed: i) an area extending from 9p22.3 to 9p22.2 that was previously identified as a critical region for the 9p duplication syndrome; ii) a region extending from 9p22.1 to 9p13.1 that was previously reported to be duplicated in a normal individual; and iii) a potential ASD locus extending from 9p24.3 to 9p23. The ASD candidate locus contained 34 genes that may contribute to the autistic features in this patient.

Conclusion: We identified a potential ASD locus (9p24.3 to 9p23) that may encompass gene(s) contributing to autism or ASD.

Citing Articles

Copy number variations in autistic children.

Alhazmi S, Alharthi M, Alzahrani M, Alrofaidi A, Basingab F, Almuhammadi A Biomed Rep. 2024; 21(1):107.

PMID: 38868529 PMC: 11168027. DOI: 10.3892/br.2024.1795.

Analysis of Faecal Microbiota and Small ncRNAs in Autism: Detection of miRNAs and piRNAs with Possible Implications in Host-Gut Microbiota Cross-Talk.

Chiappori F, Cupaioli F, Consiglio A, Di Nanni N, Mosca E, Licciulli V Nutrients. 2022; 14(7).

PMID: 35405953 PMC: 9000903. DOI: 10.3390/nu14071340.

Prenatal detection of terminal 9p24.3 microduplication encompassing DOCK8 gene: A variant of likely benign.

Yue F, Yu Y, Zhang X, Jiang Y, Li L, Liu R Medicine (Baltimore). 2021; 100(3):e23967.

PMID: 33545980 PMC: 7837864. DOI: 10.1097/MD.0000000000023967.

Rare genetic variants in the gene encoding histone lysine demethylase 4C (KDM4C) and their contributions to susceptibility to schizophrenia and autism spectrum disorder.

Kato H, Kushima I, Mori D, Yoshimi A, Aleksic B, Nawa Y Transl Psychiatry. 2020; 10(1):421.

PMID: 33279929 PMC: 7719193. DOI: 10.1038/s41398-020-01107-7.

Genotype-phenotype correlation in 75 patients with small supernumerary marker chromosomes.

Li T, Sang H, Chu G, Zhang Y, Qi M, Liu X Mol Cytogenet. 2020; 13:30.

PMID: 32684981 PMC: 7362453. DOI: 10.1186/s13039-020-00494-2.

References

Temtamy S, Kamel A, Ismail S, Helmy N, Aglan M, El Gammal M . Phenotypic and cytogenetic spectrum of 9p trisomy. Genet Couns. 2007; 18(1):29-48. View

Baccichetti C, Lenzini E, Forabosco A, Baroncini A, Dordo B, Mengarda G . [The syndrome of trisomy 9p and presentation of 2 new cases]. Pathologica. 1979; 71(1013):347-8. View

Zadeh T, Funderburk S, Carrel R, DUMARS K . 9p duplication confirmed by gene dosage effect: report of two patients. Ann Genet. 1981; 24(4):242-4. View

Vorstman J, Staal W, van Daalen E, van Engeland H, Hochstenbach P, Franke L . Identification of novel autism candidate regions through analysis of reported cytogenetic abnormalities associated with autism. Mol Psychiatry. 2005; 11(1):1, 18-28. DOI: 10.1038/sj.mp.4001781. View

Stumm M, Musebeck J, Tonnies H, Volleth M, Lemke J, Chudoba I . Partial trisomy 9p12p21.3 with a normal phenotype. J Med Genet. 2002; 39(2):141-4. PMC: 1735042. DOI: 10.1136/jmg.39.2.141. View

Weiss L, Shen Y, Korn J, Arking D, Miller D, Fossdal R . Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008; 358(7):667-75. DOI: 10.1056/NEJMoa075974. View

Newschaffer C, Croen L, Daniels J, Giarelli E, Grether J, Levy S . The epidemiology of autism spectrum disorders. Annu Rev Public Health. 2007; 28:235-58. DOI: 10.1146/annurev.publhealth.28.021406.144007. View

Bonaglia M, Giorda R, Carrozzo R, Roncoroni M, Grasso R, Borgatti R . 20-Mb duplication of chromosome 9p in a girl with minimal physical findings and normal IQ: narrowing of the 9p duplication critical region to 6 Mb. Am J Med Genet. 2002; 112(2):154-9. DOI: 10.1002/ajmg.10699. View

Szatmari P, Paterson A, Zwaigenbaum L, Roberts W, Brian J, Liu X . Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet. 2007; 39(3):319-28. PMC: 4867008. DOI: 10.1038/ng1985. View

10.

Vinci G, Chantot-Bastaraud S, El Houate B, Lortat-Jacob S, Brauner R, McElreavey K . Association of deletion 9p, 46,XY gonadal dysgenesis and autistic spectrum disorder. Mol Hum Reprod. 2007; 13(9):685-9. DOI: 10.1093/molehr/gam045. View

11.

Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T . Strong association of de novo copy number mutations with autism. Science. 2007; 316(5823):445-9. PMC: 2993504. DOI: 10.1126/science.1138659. View

12.

de Pater J, Ippel P, Van Dam W, Loneus W, Engelen J . Characterization of partial trisomy 9p due to insertional translocation by chromosomal (micro)FISH. Clin Genet. 2002; 62(6):482-7. DOI: 10.1034/j.1399-0004.2002.620611.x. View

13.

Motegi T, Watanabe K, Nakamura N, Hasegawa T, Yanagawa Y . De novo tandem duplication 9p (p12----p24) with normal GALT activity in red cells. J Med Genet. 1985; 22(1):64-6. PMC: 1049380. DOI: 10.1136/jmg.22.1.64. View

14.

Rethore M, LARGET-PIET L, Abonyi D, BOESWILLWALD M, Berger R, Carpentier S . [4 cases of trisomy for the short arm of chromosome 9. Individualization of a new morbid entity]. Ann Genet. 1970; 13(4):217-32. View

15.

Craddock N, ODonovan M, Owen M . Psychosis genetics: modeling the relationship between schizophrenia, bipolar disorder, and mixed (or "schizoaffective") psychoses. Schizophr Bull. 2009; 35(3):482-90. PMC: 2669589. DOI: 10.1093/schbul/sbp020. View

16.

Hulten M, Patel S, Tankimanova M, Westgren M, Papadogiannakis N, Maria Jonsson A . On the origin of trisomy 21 Down syndrome. Mol Cytogenet. 2008; 1:21. PMC: 2564957. DOI: 10.1186/1755-8166-1-21. View

17.

Cuoco C, Gimelli G, Pasquali F, Poloni L, Zuffardi O, Alicata P . Duplication of the short arm of chromosome 9. Analysis of five cases. Hum Genet. 1982; 61(1):3-7. DOI: 10.1007/BF00291321. View

18.

Glessner J, Wang K, Cai G, Korvatska O, Kim C, Wood S . Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. 2009; 459(7246):569-73. PMC: 2925224. DOI: 10.1038/nature07953. View

19.

Qiu S, Korwek K, Weeber E . A fresh look at an ancient receptor family: emerging roles for low density lipoprotein receptors in synaptic plasticity and memory formation. Neurobiol Learn Mem. 2005; 85(1):16-29. DOI: 10.1016/j.nlm.2005.08.009. View

20.

Klauck S . Genetics of autism spectrum disorder. Eur J Hum Genet. 2006; 14(6):714-20. DOI: 10.1038/sj.ejhg.5201610. View