Variants - Diamond-Blackfan Anemia - Leiden Open Variation Database

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This detailed view shows all details of the selected patient, including all variants reported in this patient. At the bottom of the page, all variants reported in this patient are listed, with the one you are looking at in bold. The link to the UCSC Genome Browser will show the browser zoomed in to the location of the selected variant.

Patient data (#0000086)
Patient ID	pat5rps1900028
Gender	na
Malformations	Not available
Growth Retardation	na
Steroid Response	na
Complications	-
Variant Origin	familial
Reference	Gazda et al (2004) Br J Haematol 127, 105-13
Template	DNA
Technique	SEQ
Remarks	-
# Reported	1

Variant data
Allele	Unknown
Reported pathogenicity	Pathogenic
Concluded pathogenicity	Pathogenic
Exon	04
DNA change	c.185G>A (View in UCSC Genome Browser, Ensembl)
RNA change	-
Protein	p.Arg62Gln
Frequency	-
DB-ID	RPS19_00028
Location	-
Remarks	Missense mutation; Leucine not effective in increasing translational efficiency in lymphocytes.
Molecula Mechanisms	CpG
Functional_Classific	Impairs ribosomal association but not nucleolar localization
mRNA_Expression	-
Protein_Expression	Apparently normal protein levels. Intermediate stability (HEK293) [1]
Protein_Localization	Nucleolar localization, but no ribosome association (HeLa-HEK293) [1]. It alters the ultrastructural nucleolar organization in dermal fibroblasts [2]
rRNA_Metabolism	18S rRNA processing defect both in yeast (orthologue mutation: p.Arg63Gln) and in human dermal fibroblasts, as indicated by increase in 21S pre-rRNA [2,3]. Accumulation of 45S and 41S precursors is observed in dermal fibroblasts [2]; yeast cells show nucleolar accumulation of pre-40S particles [3]
Protein_Synthesis	Translation rate reduced to 56% of controls after transfection in K562 cells [4]. In lymphocytes, translation is reduced to 66% of controls in basal conditions and to 62% after PHA activation [4]
Cell_Growth	The human mutation impairs growth of skin fibroblasts [2] and the yeast orthologue mutation (p.Arg63Gln) impairs but does not abolish cell growth in yeast [3]
Functional_Remarks	translation was found reduced in lymphocytes from all the DBA subjects studied irrespective of the presence of RPS19 mutations [4]
Functional_Reference	[1] Angelini et al (2007) Hum Mol Genet 16, 1720-7; [2]Choesmel et al (2007) Blood 109, 1275-83; [3] Léger-Silvestre et al (2005) J Biol Chem 280, 38177-85; [4] Cmejlova et al (2006) Haematologica 91, 1456-64

1 entry in RPS19

Path.

Allele

Exon

DNA change

RNA change

Protein

Frequency

DB-ID

Location

Remarks

Molecula Mechanisms

Functional_Classific

mRNA_Expression

Protein_Expression

Protein_Localization

rRNA_Metabolism

Protein_Synthesis

Cell_Growth

Functional_Remarks

Functional_Reference

+/+

Unknown

c.185G>A

p.Arg62Gln

RPS19_00028

Missense mutation; Leucine not effective in increasing translational efficiency in lymphocytes.

CpG

Impairs ribosomal association but not nucleolar localization

Apparently normal protein levels. Intermediate stability (HEK293) [1]

Nucleolar localization, but no ribosome association (HeLa-HEK293) [1]. It alters the ultrastructural nucleolar organization in dermal fibroblasts [2]

18S rRNA processing defect both in yeast (orthologue mutation: p.Arg63Gln) and in human dermal fibroblasts, as indicated by increase in 21S pre-rRNA [2,3]. Accumulation of 45S and 41S precursors is observed in dermal fibroblasts [2]; yeast cells show nucleolar accumulation of pre-40S particles [3]

Translation rate reduced to 56% of controls after transfection in K562 cells [4]. In lymphocytes, translation is reduced to 66% of controls in basal conditions and to 62% after PHA activation [4]

The human mutation impairs growth of skin fibroblasts [2] and the yeast orthologue mutation (p.Arg63Gln) impairs but does not abolish cell growth in yeast [3]

translation was found reduced in lymphocytes from all the DBA subjects studied irrespective of the presence of RPS19 mutations [4]

[1] Angelini et al (2007) Hum Mol Genet 16, 1720-7; [2]Choesmel et al (2007) Blood 109, 1275-83; [3] Léger-Silvestre et al (2005) J Biol Chem 280, 38177-85; [4] Cmejlova et al (2006) Haematologica 91, 1456-64

Diamond-Blackfan Anemia

ribosomal protein S19 (RPS19)