Table 2

Genotyping patients with classified IBMFSs and unknown genes

Clinical diagnosisNumber
tested
Number
genotyped
Mutated genesNumber of cases with mutations in this geneType of mutations in this geneNumber of alleles with this type of mutation
DBA2316RPS26 (het)5Indel/frameshift2
Start code lost2
Splicing1
RPL11 (het)3Indel/frameshift3
RPS24 (het)2Start code lost1
Splicing1
RPS19 (het)3Splicing1
Missense1
Nonsense1
RPL35A (het)1Indel/inframe1
RPS7 (het)1Missense1
SBDS (combined)1Missense1
Splicing1
FA129FANCA (hom or combined)4Missense1
Indel/frameshift4
Nonsense2
Splicing1
FANCA/BRIP1 (hom)2Nonsense4
FANCE (hom)1Missense2
FANCQ/ERCC4 (hom)1Missense2
TINF2 (het)1Missense1
SCN104ELANE (het)3Missense3
HAX1 (hom)1Nonsense2
CN73ELANE (het)3Missense2
Indel/frameshift1
FT44MYH9 (het)1Missense1
ANKRD26 (het)1Indel/frameshift1
TERT (het)2Splicing2
DC52RTEL1 (combined)1Missense1
Indel/frameshift1
TERC (combined)1ncRNA2
TAR22RBM8A*25′-UTR2
Large deletion*2
CDA22CDAN1 (combined)2Missense4
SDS†51SBDS (combined)1Indel/frameshift1
Splicing1
CSA21SLC25A38 (hom)1Missense2
Radioulnar dysostosis10
Reticular dysgenesis10
CAMT10
Total75444462‡
  • *Focused analysis of the NGS data at the RBM8A gene locus using the SureCall CNV algorithm identified a large deletion on the allele without the mutation (see online supplementary figures 42 and 43). This confirmed a compound heterozygosity state, which is the commonest genotype combination in this disease.

  • †Four of the patients with SDS had previous SBDS testing by Sanger sequencing in a clinical lab, which was negative. No mutations in other IBMFS genes were identified in these patients. A fifth patient had no prior testing for the SBDS gene; this patient was identified to have two SBDS mutations by the panel.

  • ‡The total number of 62 mutant alleles includes two large deletions that were detected by focused analysis of the NGS data at the RBM8A gene using the SureCall CNV algorithm.

  • AD, autosomal dominant; AR, autosomal recessive; CAMT, congenital amegakaryocytic thrombocytopenia; CDA, congenital dyserythropoietic anaemia; CSA, congenital sideroblastic anaemia; CN, cyclic neutropenia; DBA, Diamond–Blackfan anaemia; DC, dyskeratosis congenita; FA, Fanconi anaemia; FT, familial thrombocytopenia; IBMFSs, inherited bone marrow failure syndromes; ncRNA, non-coding RNA; NGS, next-generation sequencing; SCN, severe congenital neutropenia; SDS, Shwachman–Diamond syndrome; TAR, thrombocytopenia with absent radii.