Characterization of Genomic Variants inCSH1andGH2, Two Candidate Genes for Silver-Russell Syndrome in 17q24-q25
- 1 September 2003
- journal article
- case report
- Published by Mary Ann Liebert Inc in Genetic Testing
- Vol. 7 (3) , 259-263
- https://doi.org/10.1089/109065703322537304
Abstract
Silver-Russell syndrome (SRS) is a syndrome of severe pre- and postnatal growth retardation and typical dysmorphic features. Rare chromosomal aberrations have been reported in SRS; among these are two balanced translocations involving 17q24-q25. Recently, we described a patient with a paternally inherited heterozygous deletion of the chorionic somatomammotropin hormone 1 (CSH1) gene. The CSH1 gene is member of the growth hormone (GH) gene cluster on 17q, which consists of two growth hormone genes and three CSH genes. Genomic alterations in the GH cluster are well known, causing different phenotypes depending on the size of the deletion and the genes involved. By screening 63 SRS cases with marker D17S254, we have detected 2 further patients with a heterozygous deletion in the GH cluster. Quantitative analysis using restriction assays confirmed these findings. Additionally, in a cohort of 17 patients with isolated intrauterine and postnatal growth retardation, we detected a further patient to be carrier of a CSH1 deletion. Screening of 141 unrelated controls revealed hemizygosity in one person for which data on growth were not available. We additionally analyzed our cohort of SRS patients for mutations in CSH1 and its 3′ neighbour GH2. However, analyses failed to reveal any pathogenic mutation. While the central role of GH1 in human growth is well established, the physiological roles of CSH1 and other components of the cluster are unclear. The increased prevalence of hemizygosity of CSH1 in our population in comparison to controls indicates a role for CSH1 haploinsufficiency in the etiology of growth retardation. Investigation of CSH1 deletions in further SRS and growth retarded patients will enable us to establish under which circumstances haploinsufficiency of CSH1 is likely to result in clinical changes.Keywords
This publication has 19 references indexed in Scilit:
- Silver-Russell syndrome: a dissection of the genetic aetiology and candidate chromosomal regionsJournal of Medical Genetics, 2001
- Genomic structure of karyopherin ?2 ( KPNA2 ) within a low-copy repeat on chromosome 17q23-q24 and mutation analysis in patients with Russell-Silver syndromeHuman Genetics, 2001
- The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndromeHuman Molecular Genetics, 2000
- Paternally inherited deletion of CSH1 in a patient with Silver-Russell syndrome.Journal of Medical Genetics, 1998
- Growth and symptoms in Silver-Russell syndrome: Review on the basis of 386 patientsEuropean Journal of Pediatrics, 1995
- Severe Silver‐Russell syndrome and translocation (17;20) (q25;q13)Clinical Genetics, 1992
- CLINICAL COUNTERPOINT: The Physiology of Placental Lactogen in Human Pregnancy*Endocrine Reviews, 1991
- Placental Lactogen and Growth Hormone Receptors in Human Fetal Tissues: Relationship to Fetal Plasma Human Placental Lactogen Concentrations and Fetal Growth*Journal of Clinical Endocrinology & Metabolism, 1988
- Absence of human chorionic somatomammotropin during pregnancy associated with two types of gene deletionHuman Genetics, 1986