Other entities represented in this entry:
HGNC Approved Gene Symbol: RPS17
Cytogenetic location: 15q25.2 Genomic coordinates (GRCh38): 15:82,536,750-82,540,457 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 15q25.2 | Diamond-Blackfan anemia 4 | 612527 | Autosomal dominant | 3 |
Chen et al. (1986) cloned a human ribosomal protein S17 (RPS17) cDNA. The deduced RPS17 protein has 135 amino acids. The authors reported that the RPS17 gene appears to have been stringently conserved during evolution.
By screening a human genomic library with an RPS17 cDNA, Chen and Roufa (1988) isolated the functional RPS17 gene and 2 processed RPS17 pseudogenes.
Chen and Roufa (1988) determined that the functional RPS17 gene contains 5 exons spanning 4 kb.
By assessing the expression of RPS17 mRNA in rodent/human hybrid cells carrying different human chromosomes, Filipenko et al. (1995) mapped the functional RPS17 gene to chromosome 15. Kenmochi et al. (1998) mapped the functional RPS17 gene to 15q by somatic cell hybrid and radiation hybrid mapping analyses using an STS derived from an RPS17 intron.
Nakamichi et al. (1986) mapped the RPS17A, or RPS17L1, gene to 5q33-qter and the RPS17B, or RPS17L2, gene to 17q. Chen and Roufa (1988) stated that the RPS17A and RPS17B genes are not transcriptionally active.
In a 31-year-old Czech man with Diamond-Blackfan anemia (DBA4; 612527), Cmejla et al. (2007) identified a heterozygous mutation abolishing the translation initiation start codon of the RPS17 gene (180472.0001). The mutation was not found in his apparently healthy brother and parents or in 71 controls.
In a male patient with DBA, Gazda et al. (2008) identified heterozygosity for a 2-bp deletion in the RPS17 gene (180472.0002).
Landowski et al. (2013) performed array CGH for copy number variation in 87 probands with Diamond-Blackfan anemia who were negative for mutation in 10 known DBA-associated ribosomal protein genes and identified 2 nearly identical large deletions involving exons 3, 4, and 5 of the RPS17 gene (180472.0003) in 2 male patients.
Mammalian ribosomal protein genes are members of multigene families that are composed predominantly of multiple processed pseudogenes and one functional intron-containing gene, which has made the identification and mapping of the functional ribosomal protein genes difficult. Using an intron-containing PCR product for the analysis of rodent/human somatic cell hybrids, Feo et al. (1992) incorrectly mapped the RPS17 gene to chromosome 11pter-p13.
In a 31-year-old Czech man with Diamond-Blackfan anemia-4 (DBA4; 612527), Cmejla et al. (2007) identified a heterozygous 2T-G transversion in exon 1 of the RPS17 gene, causing a met1-to-arg (M1R) substitution that abolishes the ATG translation initiation start codon and is predicted to result in a short peptide of only 4 amino acids, beginning at the next downstream start codon at position +158. The presence of the mutation was confirmed in peripheral blood mononuclear cells, buccal swab, and nails of the patient, and was not found in his apparently healthy brother and parents or in 71 controls.
In a male patient with Diamond-Blackfan anemia (DBA4; 612527) who was diagnosed at 4 months of age and had no associated malformations, Gazda et al. (2008) identified heterozygosity for a 2-bp deletion (200delGA) in exon 3 of the RPS17 gene, resulting in a frameshift causing a termination sequence at codon 86. The mutation was not found in his unaffected parents or sister, or in at least 150 controls.
In 2 male patients with Diamond-Blackfan anemia (DBA4; 612527), Landowski et al. (2013) identified heterozygosity for a 2,887-bp and a 2,921-bp deletion at chr15:81,002,660-81,005,546 and chr15:81,002,660-81,005,580 (NCBI36), respectively, containing exons 3, 4, and 5 of the RPS17 gene. One patient was transfusion dependent, whereas the other required red blood cell transfusions 2 to 3 times a year between ages 6 weeks and 6 years, then entered remission; the latter patient was also diagnosed with developmental delay. In his unaffected parents, mPCR showed ratios similar to those of control, indicating that the mutation arose de novo in this patient; DNA was not available from both parents of the other patient. Because mPCR showed reduction of all 5 exons in both patients compared to controls, whereas only exons 3, 4, and 5 were deleted by array CGH, Landowski et al. (2013) performed copy number assay on patient DNA samples. This showed a 50% reduction of RPS17 DNA in both probands compared to the unaffected parents and controls, indicating deletion of 2 out of 4 copies of RPS17 in both.
In 2 Caucasian sibs with Diamond-Blackfan anemia-4 (DBA4; 612527), Gerrard et al. (2013) identified a heterozygous c.159T-G transversion in exon 3 of the RPS17 gene, resulting in a tyr53-to-ter (Y53X) substitution. One sib was diagnosed at birth, whereas the other sib was diagnosed at age 11 months. One had growth retardation and atrial septal defect; the other had hernia, neutropenia, and high erythrocyte adenosine deaminase in cord blood. Both were treated successfully with steroids. These patients were ascertained from a cohort of 19 patients with DBA who were screened for mutations in 80 ribosomal protein genes.
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