Construction of a Detailed Physical and Transcript Map of the Candidate Region for Russell–Silver Syndrome on Chromosome 17q23–q24

doi:10.1006/geno.2000.6413

Genomics

Volume 71, Issue 2, 15 January 2001, Pages 174-181

https://doi.org/10.1006/geno.2000.6413 Get rights and content

Abstract

Russell–Silver syndrome (RSS) is a heterogeneous disorder characterized mainly by pre- and postnatal growth retardation and characteristic dysmorphic features. The genetic cause of this syndrome is unknown. However, two autosomal translocations involving chromosome 17q25 were reported in association with RSS. Molecular analysis of the breakpoint on chromosome 17 of the de novo translocation previously described as t(1;17)(q31;q25) enabled us to refine the localization of the chromosome 17 breakpoint to 17q23–q24. Since no detailed mapping data were available for this region, we established a contig of yeast artificial chromosomes, P1 artificial chromosomes, bacterial artificial chromosomes, and cosmid clones for a 17q segment flanked by the sequence-tagged site (STS) markers D17S1557 and D17S940. This contig covers a physical distance of 4–5 Mb encompassing several novel markers. A transcript map was constructed by assigning genes and expressed sequence tags to the clone contig, and altogether 74 STS markers were mapped. Furthermore, the locus order and content provide insight into several duplication events that have occurred in the chromosomal region 17q23–q24. On the basis of our refined map, we have reduced the translocation breakpoint region to 65 kb between the newly derived markers 58T7 and CF20b. These data provide the molecular tools for the final identification of the RSS gene in 17q23–q24.

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Cited by (31)

Epigenetics in Silver-Russell syndrome
2008, Best Practice and Research: Clinical Endocrinology and Metabolism
Citation Excerpt :
To date, disruption of normal imprinting patterns due to UPD has been shown to be involved in several syndromes: Prader-Willi syndrome (maternal UPD15); Angelman syndrome (paternal UPD15); Beckwith-Wiedemann syndrome (BWS, OMIM 130650, segmental paternal UPD11p15.5); transient neonatal diabetes mellitus (paternal UPD6); maternal UPD14 syndrome; paternal UPD14 syndrome; and SRS (maternal UPD7).31 Various cytogenetic abnormalities involving chromosomes 7, 8, 11, 15, 17 and 18 have been described in a small number of SRS or SRS-like cases.32–43 Although mainly sporadic, familial SRS cases have been reported with different modes of inheritance.44
Silver-Russell syndrome (SRS) is a clinically heterogeneous syndrome characterized by intra-uterine and postnatal growth retardation with spared cranial growth, dysmorphic features and frequent body asymmetry. Various cytogenetic abnormalities have been described in a small number of SRS or SRS-like cases involving chromosomes 7, 8, 11, 15, 17 and 18. However, until recent data became available involving imprinted genes on chromosome 7 and chromosome 11p15, the molecular cause of the syndrome was unknown in most cases. Genomic imprinting is the best example of transcriptional control of genes by epigenetic modifications. Many imprinted genes play key roles in fetal and placental growth and behaviour. This is illustrated in SRS, which can now be considered as a new imprinting disease model. These new findings in the pathophysiology of SRS allow long-term follow-up studies to be performed based on molecular diagnosis. This could help to define appropriate clinical guidelines regarding growth and feeding difficulties.
Growth retardation versus overgrowth: Silver-Russell syndrome is genetically opposite to Beckwith-Wiedemann syndrome
2008, Trends in Genetics
Citation Excerpt :
Based on balanced translocations in two patients involving 17q24-q25 [8,9], a central role of this chromosomal region in SRS aetiology had long been discussed. However, characterisation of the 17q breakpoints in both patients showed that they were not identical [10]. Recently Dörr et al. [11] found that the karyopherin α2 (KPNA2) gene lies in one of the breakpoints in 17q, but they excluded the involvement of this candidate gene in the aetiology of SRS.
Human growth is a complex process that requires the appropriate interaction of many players. Central members in the growth pathways are regulated epigenetically and thereby reflect the profound significance of imprinting for correct mammalian ontogenesis. In this review, we show that the growth retardation disorder Silver-Russell syndrome (SRS) is a suitable model to decipher the role of imprinting in growth. As we will show, SRS should not only be regarded as the genetically (and clinically) opposite disease to Beckwith-Wiedemann syndrome, but it also represents the first human disorder with imprinting disturbances that affect two different chromosomes (i.e. chromosomes 7 and 11). Thus, a functional interaction between factors encoded by chromosomes 7 and 11 is likely.
Gal2 galanin receptor
2007, xPharm: The Comprehensive Pharmacology Reference
The GAL2 receptor is activated by the endogenous peptides galanin and galanin-like peptide (GALP) and is a member of the galanin receptor family. Currently, a total of three subtypes of galanin receptors, referred to as GAL1 (GalR1), GAL2 (GalR2), and GAL3 (GalR3), have been cloned from several species (human, rat, mouse). Each receptor subtype has a high sequence homology between different species, but within species the similarities between different receptor subtypes are lower. GAL2 is found in nervous and non-nervous tissues. A few synthetic peptide ligands have high, selective affinity for GAL2 and the pharmacology of the GAL2 has been best characterized in vitro, although some recent studies have demonstrated GAL2-mediated actions in vivo.
Hypomethylation of the H19 gene causes not only silver-russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype
2006, American Journal of Human Genetics
The H19 differentially methylated region (DMR) controls the allele-specific expression of both the imprinted H19 tumor-suppressor gene and the IGF2 growth factor. Hypermethylation of this DMR—and subsequently of the H19 promoter region—is a major cause of the clinical features of gigantism and/or asymmetry seen in Beckwith-Wiedemann syndrome or in isolated hemihypertrophy. Here, we report a series of patients with hypomethylation of the H19 locus. Their main clinical features of asymmetry and growth retardation are the opposite of those seen in patients with hypermethylation of this region. In addition, we show that complete hypomethylation of the H19 promoter is found in two of three patients with the full clinical spectrum of Silver-Russell syndrome. This syndrome is also characterized by growth retardation and asymmetry, among other clinical features. We conclude that patients with these clinical features should be analyzed for H19 hypomethylation.
Nuclear MRP genes and mitochondrial disease
2005, Gene
The ancestral mitochondrial ribosome (70S) underwent major structural remodeling during the evolution of mammalian mitochondrial ribosomes (55S). Despite the loss of nearly half their RNA, 55S ribosomes are actually larger than bacterial ribosomes because of all the extra proteins they contain. Typical of mammalian mitochondrial ribosomes, the human mitochondrial ribosome is one of the most protein-rich ribosomes, containing several new proteins. One of the new proteins is a novel GTP binding protein, DAP3, that has been implicated in apoptosis. Except for DAP3, the locations of the individual new proteins in the ribosome are unknown. All of the MRPs are encoded by nuclear genes. Mutations or deficiencies of ribosome assembly proteins or other essential proteins are candidates for mitochondrial disease, since the mitochondrial ribosome translates mRNAs for the 13 essential components of the oxidative phosphorylation system. Several of the MRP genes map to loci associated with disorders consistent with impaired oxidative phosphorylation, such as Leigh Syndrome, multiple mitochondrial dysfunctions, and non-syndromic hearing loss. This manuscript reviews the distinctive properties of human mitochondrial ribosomes and ribosomal proteins, and the correlation of MRP3 gene locations with loci associated with disorders of energy metabolism, and provides localization information for one of the unusual proteins contained in human mitochondrial ribosomes, MRPS29.
Paternal reciprocal translocation t(11;16)(p13;q24.3) in a Silver-Russel syndrome patient
2003, Annales de Genetique
Citation Excerpt :
A hemizygous deletion of the insulin-like growth factor receptor gene (IGFIR) localised to 15q26.3 was identified in SRS patients [15]. Two patients with severe SRS described with reciprocal translocation involving distal chromosome 17q with the breakpoint originally localised to 17q25 [16]. Two members of the growth factor receptor protein (GRB) family of genes GRB2 and GRB7 which map to 17q25.1 and 17q21.1, respectively, have been analysed as candidates for SRS.
We describe a 7-month-old male child with Silver–Russel syndrome (SRS) phenotype, presented with two major clinical features: low birth weight, short stature, and minor features, such as macrocephaly, clinodactyly, essential for the diagnosis of SRS. Routine cytogenetic studies with GTG-banding showed 46,XY,t(11;16)(p13;q24.3). Fluorescence in situ hybridisation (FISH) with single copy probes BAC (11p13) and PAC (16q24.3), showed a reciprocal translocation. Chromosomal analysis of the mother was normal and the phenotypically normal father had apparently identical translocation t(11;16)(p13;q24.3). The disruption of growth factor genes at 11p and 16q breakpoint regions due to reciprocal translocation in the father might have caused SRS phenotype in the child.

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¹: Current address: Ingenium Pharmaceuticals AG, Lochhamer Strasse 29, 82152 Martinsried, Germany.

²: To whom correspondence should be addressed. Telephone: +49/345/5574291. Fax: +49/345/5574293. E-mail: [email protected].

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Regular ArticleConstruction of a Detailed Physical and Transcript Map of the Candidate Region for Russell–Silver Syndrome on Chromosome 17q23–q24

Abstract

J. Pediat.

Genomics

Cancer Genet. Cytogenet.

Am. J. Hum. Genet.

Am. J. Hum. Genet.

Biochem. Biophys. Res. Commun.

Am. J. Hum. Genet.

Autosomal dominant Russell–Silver syndrome

Am. J. Med. Genet.

Molecular cytogenetic mapping of 24 CEPH YACs and 24 gene-specific large insert probes to chromosome 17

Cytogenet. Cell Genet.

Increased copy number at 17q22–q24 by CGH in breast cancer is due to high-level amplification of two separate regions

Genes Chromosomes Cancer

Identification of three novel Ca(2+) channel gamma subunit genes reveals molecular diversification by tandem and chromosome duplication

Genome Res.

Deletion short arm 18 and Silver–Russell syndrome

Acta Paediatr. Scand.

RAG-1 interacts with the repeated amino acid motif of the human homologue of the yeast protein SRP1

Proc. Natl. Acad. Sci. USA

Rch1, a protein that specifically interacts with the RAG-1 recombination-activating protein

Proc. Natl. Acad. Sci. USA

Adolescent growth and pubertal progression in the Silver–Russell syndrome

Arch. Dis. Child.

A comprehensive genetic map of the human genome based on 5,264 microsatellites

Nature

Report of the First International Workshop on Human Chromosome 15 Mapping

Cytogenet. Cell. Genet.

Three-generation dominant transmission of the Silver–Russell syndrome

Am. J. Med. Genet.

Molecular studies in 37 Silver–Russell syndrome patients: Frequency and etiology of uniparental disomy

Hum. Genet.

Nucleocytoplasmic transport

Science

A new bacteriophage P1-derived vector for the propagation of large human DNA fragments

Nat. Genet.

Duplication of 7p12.1–p13, including GRB10 and IGFBP1, in a mother and daughter with features of Silver–Russell syndrome

Hum. Genet.

Russell–Silver syndrome (RSS) associated with dup(1)(q42 → qter)

Clin. Genet.

Evidence for distinct substrate specificities of importin alpha family members in nuclear protein import

Mol. Cell. Biol.

Uniparental disomy 7 in Silver–Russell syndrome and primordial growth retardation

Hum. Mol. Genet.

Prenatal and postnatal growth failure associated with maternal heterodisomy for chromosome 7

J. Med. Genet.

Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries

Hum. Genet.

Regular Article
Construction of a Detailed Physical and Transcript Map of the Candidate Region for Russell–Silver Syndrome on Chromosome 17q23–q24