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
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
Aucun commentaire:
Enregistrer un commentaire