Translocation déséquilibrée de novo (duplication 4p / suppression 8p) chez un patient avec autisme, TOC et syndrome de croissance excessive

Aperçu: G.M.

Des anomalies chromosomiques, telles que des translocations non équilibrées et des variations du nombre de copies (CNV), se retrouvent dans les troubles du spectre de l'autisme.

Les translocations impliquant les chromosomes 4 et 8 sont peut-être la deuxième translocation la plus fréquente chez l'homme et ne sont souvent pas détectées dans la cytogénétique de routine.

La région 8p23.3 contient le gène candidat DLGAP2, qui peut contribuer à l'autisme lorsqu'il est perturbé. Il y a eu un rapport indépendant d'un patient avec autisme, un trouble obsessionnel compulsif (TOC), un trouble de l'hyperactivité avec déficit de l'attention (TDAH) et un syndrome de surcroissance, dont la translocation non équilibrée de novo (8) t (4; 8) p ( 16.1 → ter; 23.1 → ter) a été initialement manquée par la cytogénétique de routine, mais détectée avec un microprogramme SNP, permettant une résolution plus élevée des points d'arrêt de la translocation. 

Am J Med Genet A. 2017 Apr 13. doi: 10.1002/ajmg.a.38171.

De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome

Sagar A^1,2, Pinto D^3,4, Najjar F², Guter SJ², Macmillan C⁵, Cook EH².

Author information

1

Division of Psychiatry and Behavioral Sciences, Children's National Medical Center, Washington, District of Columbia.

2

Institute for Juvenile Research, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois.

3

The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.

4

Departments of Psychiatry, and Genetics and Genomic Sciences, Seaver Autism Center, The Mindich Child Health & Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York.

5

Department of Pediatrics, University of Chicago, Chicago, Illinois.

Abstract

Chromosomal abnormalities, such as unbalanced translocations and copy number variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al. () Neuron 70: 863-885]. Many chromosomal abnormalities, including sub microscopic genomic deletions and duplications, are missed by G-banded karyotyping or Fragile X screening alone and are picked up by chromosomal microarrays [Shen et al. () Pediatrics 125: e727-735]. Translocations involving chromosomes 4 and 8 are possibly the second most frequent translocation in humans and are often undetected in routine cytogenetics [Giglio et al. () Circulation 102: 432-437]. Deletions of 4p16 have been associated with Wolf-Hirschhorn syndrome while 4p16 duplications have been associated with an overgrowth syndrome and mild to moderate mental retardation [Partington et al. () Journal of Medical Genetics 34: 719-728]. The 8p23.3 region contains the autism candidate gene DLGAP2, which can contribute to autism when disrupted [Marshall et al. () The American Journal of Human Genetics 82: 477-488] . There has been a case report of a family with autism spectrum disorder (ASD), prominent obsessional behavior, and overgrowth in patients with der (8) t (4;8) p (16;23) [Partington et al. ()]. This is an independent report of a male patient with autism, obsessive compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and an overgrowth syndrome, whose de novo unbalanced translocation der (8) t (4;8) p (16.1→ter; 23.1→ter) was initially missed by routine cytogenetics but detected with SNP microarray, allowing higher resolution of translocation breakpoints.

© 2017 Wiley Periodicals, Inc.

PMID:28407363

DOI: 10.1002/ajmg.a.38171