TBR1 is the candidate gene for intellectual disability in patients with a 2q24.2 interstitial deletion

Orazio Palumbo, Marco Fichera, Pietro Palumbo, Renata Rizzo, Elisabetta Mazzolla, Donatella Maria Cocuzza, Massimo Carella, Teresa Mattina

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Interstitial deletion of 2q24.2 is a rarely described cytogenetic aberration in patients with intellectual disability (ID). Previously reported genotype-phenotype correlation identified a minimum deleted region of 2.65Mb including 15 genes. Recently, a patient with a de novo 2q24.2 microdeletion of 0.4Mb encompassing only three genes was described. However, the precise relationship between most deleted genes and the clinical features remains unclear. Here we describe a 12-year-old male patient diagnosed with growth retardation and ID. He also showed microcephaly, right palpebral ptosis, scapular winging, and pectus excavatum. Single nucleotide polymorphisms (SNP) array analysis showed a de novo interstitial deletion of 0.122Mb at 2q24.2 region harboring only TBR1 (T-box, brain, 1; OMIM: 604616), which encodes a T-box family transcription factor expressed in post-mitotic projection neurons and functionally significant in embryologic corticogenesis. This is the first case of a deletion at 2q24.2 involving only TBR1. This finding narrows the smallest region of overlap (SRO) for deletions in this region and strengthens the previously suggested hypothesis that this gene is a strong candidate for the ID phenotype. The identification of TBR1 as candidate for ID encourages further molecular studies to identify novel mutations to understand the pathogenic effects of its haploinsufficiency. Finally, this report provides a review on 10 2q24.2 microdeletion patients.

Original languageEnglish
Pages (from-to)828-833
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Volume164
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Genetic Databases
Intellectual Disability
Brain
Genes
Funnel Chest
Haploinsufficiency
Microcephaly
Genetic Association Studies
Eyelids
Chromosome Aberrations
Single Nucleotide Polymorphism
Transcription Factors
Phenotype
Neurons
Mutation
Growth

Keywords

  • 2q24.2
  • Smallest region of overlap
  • SNP Arrays analysis
  • TBR1

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

TBR1 is the candidate gene for intellectual disability in patients with a 2q24.2 interstitial deletion. / Palumbo, Orazio; Fichera, Marco; Palumbo, Pietro; Rizzo, Renata; Mazzolla, Elisabetta; Cocuzza, Donatella Maria; Carella, Massimo; Mattina, Teresa.

In: American Journal of Medical Genetics, Part A, Vol. 164, No. 3, 03.2014, p. 828-833.

Research output: Contribution to journalArticle

Palumbo, Orazio ; Fichera, Marco ; Palumbo, Pietro ; Rizzo, Renata ; Mazzolla, Elisabetta ; Cocuzza, Donatella Maria ; Carella, Massimo ; Mattina, Teresa. / TBR1 is the candidate gene for intellectual disability in patients with a 2q24.2 interstitial deletion. In: American Journal of Medical Genetics, Part A. 2014 ; Vol. 164, No. 3. pp. 828-833.
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