Microdeletion of the Down syndrome critical region at 21q22

Hideki Fujita, Chiharu Torii, Rika Kosaki, Shinya Yamaguchi, Jun Kudo, Kumiko Hayashi, Takao Takahashi, Kenjiro Kosaki

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 fromcrucial 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 3.97Mb 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.

Original languageEnglish
Pages (from-to)950-953
Number of pages4
JournalAmerican Journal of Medical Genetics, Part A
Volume152
Issue number4
DOIs
Publication statusPublished - 2010 Apr

Fingerprint

Haploinsufficiency
Microcephaly
Hypospadias
Retrognathia
Uvula
Eyebrows
Corneal Opacity
Phenotype
Comparative Genomic Hybridization
Gene Dosage
Nipples
Fetal Growth Retardation
Eyelids
Incisor
Heterozygote
Karyotype
Nose
Genes
Tooth
Central Nervous System

Keywords

  • Chromosome 21q
  • Corneal clouding
  • Down syndrome
  • Hypospadias
  • Thrombocytopenia

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Microdeletion of the Down syndrome critical region at 21q22. / Fujita, Hideki; Torii, Chiharu; Kosaki, Rika; Yamaguchi, Shinya; Kudo, Jun; Hayashi, Kumiko; Takahashi, Takao; Kosaki, Kenjiro.

In: American Journal of Medical Genetics, Part A, Vol. 152, No. 4, 04.2010, p. 950-953.

Research output: Contribution to journalArticle

Fujita H, Torii C, Kosaki R, Yamaguchi S, Kudo J, Hayashi K et al. Microdeletion of the Down syndrome critical region at 21q22. American Journal of Medical Genetics, Part A. 2010 Apr;152(4):950-953. https://doi.org/10.1002/ajmg.a.33228
Fujita, Hideki ; Torii, Chiharu ; Kosaki, Rika ; Yamaguchi, Shinya ; Kudo, Jun ; Hayashi, Kumiko ; Takahashi, Takao ; Kosaki, Kenjiro. / Microdeletion of the Down syndrome critical region at 21q22. In: American Journal of Medical Genetics, Part A. 2010 ; Vol. 152, No. 4. pp. 950-953.
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