An 8.9 Mb 19p13 duplication associated with precocious puberty and a sporadic 3.9 Mb 2q23.3q24.1 deletion containing NR4A2 in mentally retarded members of a family with an intrachromosomal 19p-into-19q between-arm insertion
| Autor: | Gunnar Houge, Harald Breilid, Christine Stansberg, Vidar M. Steen, Karen Helene Ørstavik, Trine Prescott, Helle Lybæk, Randi Hovland |
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| Rok vydání: | 2009 |
| Předmět: |
Male
Proband Formins Puberty Precocious Chromosome Disorders Biology Short stature Article Gene Duplication Intellectual Disability Chromosome 19 Nuclear Receptor Subfamily 4 Group A Member 2 Gene duplication Genetics medicine Humans Precocious puberty Family Genetics (clinical) Chromosomal inversion Chromosome Aberrations Proteins Middle Aged Microdeletion syndrome medicine.disease Pedigree DNA-Binding Proteins Mutagenesis Insertional Essential gene Child Preschool Chromosomes Human Pair 2 Female Chromosome Deletion medicine.symptom Chromosomes Human Pair 19 Transcription Factors |
| Zdroj: | European Journal of Human Genetics. 17:904-910 |
| ISSN: | 1476-5438 1018-4813 |
| DOI: | 10.1038/ejhg.2008.261 |
| Popis: | In a 2 and a half-year-old girl with onset of puberty before the age of 5 months, short stature, hand anomalies and severe mental retardation, an 8.9 Mb interstitial 19p13 duplication containing 215 predicted genes was detected. It was initially assumed that the duplication involved the kisspeptin receptor gene, GPR54, known to stimulate induction of puberty, but more refined duplication mapping excluded this possibility. In an attempt to further understand the genotype–phenotype correlation, global gene expression was measured in skin fibroblasts. The overall expression pattern was quite similar to controls, and only about 25% of the duplicated genes had an expression level that was increased by more than 1.3-fold, with no obvious changes that could explain the precocious puberty. The proband's mother carried a balanced between-arm insertion of the duplicated segment that resembled a pericentric inversion. The same insertion was found in several other family members, including one who had lost a daughter with severe mental retardation and menarche at the age of 10 years. Another close relative was severely mentally retarded, but neither dysmorphic nor microcephalic. His phenotype was initially ascribed to a presumed cryptic chromosome 19 imbalance caused by the 19p-into19q insertion, but subsequent array-CGH detected a 3.9-Mb deletion of 2q23.3q24.1. This novel microdeletion involves seven genes, of which FMNL2, a suggested regulator of Rho-GTPases, and NR4A2, an essential gene for differentiation of dopaminergic neurons, may be critical genes for the proposed 2q23q24 microdeletion syndrome. |
| Databáze: | OpenAIRE |
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