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Microdeletion of the Down syndrome critical region at 21q22
- Source :
- American journal of medical genetics. Part A. (4)
- Publication Year :
- 2010
-
Abstract
- The concept of the Down syndrome critical region implies the existence of several dosage-sensitive genes that result in an abnormal phenotype when duplicated. Among the genes in the presumed Down syndrome critical region, DYRK1A and SIM2 are thought to be particularly important because of their critical roles in the development of the central nervous system in model organisms. Considering that regulatory imbalances resulting in an altered amount of expression from crucial target genes tend to produce phenotypic effects in both monosomics and trisomics, haploinsufficiency for the Down syndrome critical region is expected to be associated with an abnormal phenotype. We report on a patient with severe microcephaly, a developmental delay, hypospadias, and corneal opacity who had a microdeletion spanning the Down syndrome critical region, including DYRK1A and SIM2. He presented with intrauterine growth retardation, hypospadias, corneal clouding, arched eyebrows, upslanting and narrow palpebral fissures, bifid uvula, prominent nasal root, short columella, prominent central incisors, pegged shaped teeth, retrognathia, hypoplastic nipples, and severe developmental delay. His G-banded karyotype was normal, but array comparative genomic hybridization showed a de novo deletion of 3.97 Mb at chromosome 21q22. The extreme degree of microcephaly in this patient may be ascribed to the haploinsufficiency of DYRK1A, since brain size is severely reduced in heterozygotes for the Dyrk1a null mutation in mice.
- Subjects :
- Male
Down syndrome
Microcephaly
Chromosomes, Human, Pair 21
Aneuploidy
Biology
Pregnancy
Genetics
medicine
Humans
Child
Genetics (clinical)
In Situ Hybridization, Fluorescence
Comparative Genomic Hybridization
Infant, Newborn
Facies
Infant
Reproducibility of Results
medicine.disease
Null allele
Palpebral fissure
Hypospadias
Child, Preschool
Female
Chromosome Deletion
Down Syndrome
Haploinsufficiency
Trisomy
Subjects
Details
- ISSN :
- 15524833
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- American journal of medical genetics. Part A
- Accession number :
- edsair.doi.dedup.....51f2e0fe72d9cd2e954048b06d8cc606