RPL35 – Diamond-Blackfan Anaemia

RPL35 encodes ribosomal protein L35 and is associated with autosomal dominant Diamond-Blackfan anaemia (MONDO:0015253). In a study of 87 families with DBA, whole‐exome sequencing identified a heterozygous c.231G>T (p.Lys77Asn) variant in one proband presenting with erythroid hypoplasia and congenital anomalies (PMID:28280134). No additional affected relatives were reported, limiting segregation evidence.

Functional studies in zebrafish demonstrate that morpholino knockdown of rpl35 leads to marked reduction of erythrocytes and developmental defects mirroring human DBA, substantiating a haploinsufficiency mechanism (PMID:18653748). The concordance between human genetic findings and zebrafish erythropoietic defects supports the pathogenic role of RPL35.

Key take‐home: Heterozygous RPL35 variants, notably p.Lys77Asn, are likely pathogenic in DBA and should be included in molecular diagnostic panels.

References

• Journal of Medical Genetics • 2017 • Novel and known ribosomal causes of Diamond-Blackfan anaemia identified through comprehensive genomic characterisation. PMID:28280134
• Human Molecular Genetics • 2008 • Deficiency of ribosomal protein S19 during early embryogenesis leads to reduction of erythrocytes in a zebrafish model of Diamond-Blackfan anemia. PMID:18653748

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