Molecular diagnosis of deletions in the human multigene complex of growth and placental lactogen hormones

González-Rodríguez, Everardo; Jaramillo‐Rangel, Gilberto; Barrera-Saldaña, Hugo A.

doi:10.1002/(sici)1096-8628(19971112)72:4<399::aid-ajmg5>3.0.co;2-m

Cited by 8 publications

(10 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 25-ml PCR volumes contained 13 PCR buffer (Gibco BRL), 1.5 mM MgCl 2 , 0.75 U Taq polymerase (Gibco BRL), and 200 mM of each dNTP. Primers used were CSH-402 (59-ggggatcctgtggacagctcaccta-39) and CSH-403 (59-ccgaattccaggagaggcactgggga-3 9) (Gonzalez- Rodriguez et al, 1997). Cycling conditions consisted of an initial denaturation at 94°C for 5 min, followed by 40 cycles including 94°C for 30 sec, 69°C for 90 sec, 72°C for 2 min, and a final extension at 72°C for 10 min.…”

Section: Molecular Studiesmentioning

confidence: 99%

“…The primer set allows the amplification of all five gene within the GH cluster; the resulting PCR products can be differentiated using the respective restriction endonucleases (Gonzalez-Rodriguez et al, 1997). Digestion with BstE II gives bands specific for CSH1.…”

Section: Molecular Studiesmentioning

confidence: 99%

“…In the cases with proven CSH1 deletions, the patients were additionally investigated for other members of the GH cluster by performing specific restriction assays, described by Gonzalez-Rodriguez (1997). For the GH1 gene, we established a realtime PCR approach to determine the GH1 copy number using an ABI Prism7000.…”

Section: Prager Et Al 260mentioning

confidence: 99%

See 2 more Smart Citations

Characterization of Genomic Variants inCSH1andGH2, Two Candidate Genes for Silver-Russell Syndrome in 17q24-q25

et al. 2003

View full text Add to dashboard Cite

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.

show abstract

Section: Molecular Studiesmentioning

confidence: 99%

Section: Molecular Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Genomic Variants inCSH1andGH2, Two Candidate Genes for Silver-Russell Syndrome in 17q24-q25

et al. 2003

View full text Add to dashboard Cite

show abstract

“…As a prior step, deletions of the GH1 gene were excluded on genomic DNA level by using a PCRbased deletion test published by Gonzalez-Rodriguez et al 10 as well as by a Real-Time PCR approach based on TaqMan™ technology 11 . Mutations in the GH1 gene were excluded by a denaturing highperformance liquid chromatography (DHPLC) assay (Pfaffle, personal communication).…”

Section: Dna Studiesmentioning

confidence: 99%

Analysis of Components of the Growth Hormone (GH) Axis in (GH Deficient) Patients with Silver-Russell Syndrome

Mavany¹,

Wollmann²,

Pfäffle³

et al. 2002

International Journal on Disability and Human Development

View full text Add to dashboard Cite

Silver-Russell syndrome (SRS) is a heterogeneous clinical syndrome with evidence for a substantial role of genetic factors in its aetiology. Disturbances of chromosome 7, i.e. duplications in 7p and uniparental disomies, have been described in more than 10% of patients; a putative SRS gene in 7p can therefore be assumed. Furthermore, in approximately 5-10% of patients with SRS a growth hormone (GH) deficiency can be observed. Since the growth hormone-releasing hormone receptor (GHRH-R) is localised in 7p and mutations in this gene are associated with GH deficiency, we screened five GH deficient SRS patients for mutations in the GHRH-R gene by direct sequencing of the whole coding region. To exclude mutations in genes of the other major members of the GH axis, growth hormone releasing hormone (GHRH) and GH itself (GH1), these genes were also investigated for genomic variations. While we did not observe variants in GH1 and GHRH, we detected three base-pair substitutions in the coding region of GHRH-R. These variants were detected in a cohort of 45 non-GH deficient SRS patients and 15 patients with isolated growth retardation as well as in 50 healthy controls. In conclusion, we exclude a major role of GHRH, GHRH-R and GH1 as central members of the GH axis in the pathogenesis of SRS.

show abstract

“…Variation of height is associated with a range of diseases, such as various cancers [2], type 2 diabetes [3], coronary heart disease [4]. Among the most visible traits that can be measured easily and accurately [5], adult human height is mainly influenced by genetic and environmental factors [6].…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Study Identified CNP12587 Region Underlying Height Variation in Chinese Females

et al. 2012

View full text Add to dashboard Cite

IntroductionHuman height is a highly heritable trait considered as an important factor for health. There has been limited success in identifying the genetic factors underlying height variation. We aim to identify sequence variants associated with adult height by a genome-wide association study of copy number variants (CNVs) in Chinese.MethodsGenome-wide CNV association analyses were conducted in 1,625 unrelated Chinese adults and sex specific subgroup for height variation, respectively. Height was measured with a stadiometer. Affymetrix SNP6.0 genotyping platform was used to identify copy number polymorphisms (CNPs). We constructed a genomic map containing 1,009 CNPs in Chinese individuals and performed a genome-wide association study of CNPs with height.ResultsWe detected 10 significant association signals for height (p<0.05) in the whole population, 9 and 11 association signals for Chinese female and male population, respectively. A copy number polymorphism (CNP12587, chr18:54081842-54086942, p = 2.41×10−4) was found to be significantly associated with height variation in Chinese females even after strict Bonferroni correction (p = 0.048). Confirmatory real time PCR experiments lent further support for CNV validation. Compared to female subjects with two copies of the CNP, carriers of three copies had an average of 8.1% decrease in height. An important candidate gene, ubiquitin-protein ligase NEDD4-like (NEDD4L), was detected at this region, which plays important roles in bone metabolism by binding to bone formation regulators.ConclusionsOur findings suggest the important genetic variants underlying height variation in Chinese.

show abstract

Molecular diagnosis of deletions in the human multigene complex of growth and placental lactogen hormones

Cited by 8 publications

References 15 publications

Characterization of Genomic Variants inCSH1andGH2, Two Candidate Genes for Silver-Russell Syndrome in 17q24-q25

Characterization of Genomic Variants inCSH1andGH2, Two Candidate Genes for Silver-Russell Syndrome in 17q24-q25

Analysis of Components of the Growth Hormone (GH) Axis in (GH Deficient) Patients with Silver-Russell Syndrome

Genome-Wide Association Study Identified CNP12587 Region Underlying Height Variation in Chinese Females

Contact Info

Product

Resources

About