An emerging 1q21.1 deletion-associated neurodevelopmental phenotype
Lina Basel-Vanagaite1, Hadassa Goldberg-Stern, Aviva Mimouni-Bloch
1Schneider Children's Medical Center of Israel, Petach Tikva, Israel. basel@post.tau.ac.il
Journal of Child Neurology
|January 8, 2011
Summary
A family presented with inherited 1q21.1 deletion causing neurodevelopmental issues and epilepsy. This microdeletion was identified using comparative genomic hybridization microarray, highlighting the need to consider genetic causes for atypical epilepsy.
Area of Science:
- Genetics
- Neurodevelopmental Disorders
- Epilepsy
Background:
- Inherited chromosomal abnormalities can lead to complex neurodevelopmental and neurological phenotypes.
- The 1q21.1 region is known to harbor deletions associated with various developmental disorders.
Purpose of the Study:
- To investigate the genetic basis of neurodevelopmental delay and atypical epilepsy in a family.
- To characterize the phenotype associated with a novel 1q21.1 microdeletion.
Main Methods:
- Case study of a proband and family members.
- Prenatal ultrasound (nuchal translucency, oligohydramnion).
- Agilent Human Genome CGH Microarray 105A for genetic analysis.
Main Results:
- The proband exhibited mild global developmental delay, ataxic gait, and complex seizures.
- A 1.65 Mb microdeletion on chromosome 1q21.1 was identified in the proband and his asymptomatic father.
- Epileptic seizures occurred despite normal interictal electroencephalogram (EEG) findings.
Conclusions:
- A 1q21.1 microdeletion can present with neurodevelopmental problems and atypical epilepsy.
- Cryptic cytogenetic abnormalities should be investigated in cases of unexplained neurodevelopmental and epileptic phenotypes, particularly with normal EEG.
- The identified deletion is larger than previously reported recurrent deletions in this region, suggesting a potentially distinct pathogenic mechanism.
Related Concept Videos
01:49Meiosis I
Meiosis is a carefully orchestrated set of cell divisions, the goal of which—in humans—is to produce haploid sperm or eggs, each containing half the number of chromosomes present in somatic cells elsewhere in the body. Meiosis I is the first such division, and involves several key steps, among them: condensation of replicated chromosomes in diploid cells; the pairing of homologous chromosomes and their exchange of information; and finally, the separation of homologous chromosomes by a...
01:19Autism Spectrum Disorder
Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by persistent deficits in social communication and interaction alongside restrictive and repetitive behaviors or interests. ASD is sometimes accompanied by intellectual impairment.
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
01:43Sex-linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
01:21Huntington Disease l: Introduction
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
01:30Neurulation
Neurulation is the embryological process which forms the precursors of the central nervous system and occurs after gastrulation has established the three primary cell layers of the embryo: ectoderm, mesoderm, and endoderm. In humans, the majority of this system is formed via primary neurulation, in which the central portion of the ectoderm—originally appearing as a flat sheet of cells—folds upwards and inwards, sealing off to form a hollow neural tube. As development proceeds, the anterior...