Table 1.

Identification of causative genetic variants in 11 patients with inherited anaemias using targeted NGS‐based panel sequencing

Patient	Age (years)	Sex	Key clinical features	Key haematological features	Gene	Mutation	Type of mutation	Inheri‐tance	Final Diagnosis	Clinical Relevance	Additional information
1	13·7	M	Jaundice, splenomegaly, gall stones	Moderate normocytic CHA with spherocytes	SPTB	NM_001024858.2:c.5961_5964delinsTTC p.M1988Sfs*7	Het, novel	AD	Hereditary spherocytosis	Confirmatory	Reduced EMA staining UGT1A1 wild‐type
2	8	F	Jaundice, splenomegaly, gall stones	Moderate normocytic CHA with spherocytes	SPTB	NM_001024858.2:c.4309dupG; p.E1437Gfs*54	Het, novel	AD	Hereditary spherocytosis	Confirmatory	Reduced EMA staining, subtotal splenectomy
3	13·6	M	Jaundice, splenomegaly, gall stones	Moderate normocytic CHA with spherocytes	ANK1	NM_001142446.1:c.457C>T p.Q153*	Het, novel	AD	Hereditary spherocytosis	Confirmatory	Reduced osmotic fragility, cholecystectomy + subtotal splenectomy at 5 years, spleen regrowth. UGT1A1 wild‐type
4	1	M	Jaundice	Moderate normocytic CHA with spherocytes	ANK1	NM_001142446.1:c.4510_4513delAACA p.N1504Wfs*17	Het, novel	AD	Hereditary spherocytosis	Confirmatory	Reduced EMA staining, transfusions until age 7 months
5	2·7	F	Jaundice	Moderate normocytic CHA with spherocytes	ANK1	NM_001142446.1:c.1872_1884delGGGCGGCTCCCCG p.G625Tfs*41	Het, novel	AD	Hereditary spherocytosis	Confirmatory	Reduced EMA staining
6	4·6	F	Jaundice, splenomegaly	Severe macrocytic CHA, dyserythropoiesis	PKLR	NM_000298.5:c.1675C>G p.R559G	Hom	AR, Con	Pyruvate kinase deficiency	Diagnostic, recommend splenectomy	PK activity low normal range, parents normal PK activity
7	19·2	M	Jaundice, splenomegaly, gall stones	Mild macrocytic CHA, dessicytes	PIEZO1	NM_001142864.2:c.7367G>A p.R2456H	Het	AD	Hereditary xerocytosis	Diagnostic, avoid splenectomy	Admitted with diagnosis of ‘familial hyperbilirubinaemia’
8	10·1	F	Jaundice, splenomegaly	Mild macrocytic CHA, dessicytes, dyserythropoiesis	PIEZO1	NM_001142864.2:c.4082A>G p.Q1361R	Het, novel	AD, de novo	Hereditary xerocytosis	Diagnostic, avoid splenectomy	UGT1A1 promotor variant aggravates jaundice
9	3·4	M	Splenomegaly	Severe macrocytic CHA, aniso‐poikilocytes; dyserythropoiesis, inter‐nuclear bridges	CDAN1	NM_138477.2:c.2044C>T p.R682* c.3575T>C p.L1192S†	Com, †novel	AR	CDA1	Diagnostic, consider interferon therapy	Transfusion dependent as infant, later on moderate anaemia
10	17·9	M	Jaundice, cardiac defects, skeletal defects	Moderate macrocytic CHA, aniso‐poikilocytes; dyserythropoiesis inter‐nuclear bridges	CDAN1	NM_138477.2:c.2015C>T p.P672L† c.1189C>T p.R397W	Com, †novel	AR	CDA1	Diagnostic, consider interferon therapy	Extramedullary haematopoiesis of the skull, Chiari 1 malformation, syringomyelia, surgery for cardiac defects in infancy
11	1·2	M	Paleness, fatigue	Severe macrocytic hyporegenerative anaemia, lack of BM erythroblasts	RPS29	NM_001032.4:c.139G>A p.A47T	Het, novel	AD	Diamond‐Blackfan anaemia	Confirmatory, offer steroid therapy	Elevated erythrocyte adenosine deaminase and HbF

AD, autosomal dominant; ANK1, ankyrin 1; AR, autosomal recessive; BM, bone marrow; CDA1, congenital dyserythro‐poietic anaemia type I; CDAN1, codanin 1; CHA, chronic haemolytic anaemia; Com, compound heterozygous; Con, consanguineous; EMA, eosin‐5′‐maleimide: F, female, FANCA, Fanconi anaemia complementation group A; GATA2, GATA binding protein 2; HbF, haemoglobin F; Het, heterozygous; Hom, homozygous; M, male, MDS, myelodysplastic syndrome; MYH9, myosin heavy chain 9; NGS, next generation sequencing; NHEJ1, non‐homologous end joining factor 1; PIEZO1, piezo type mechanosensitive ion channel component 1; PK, pyruvate kinase; PKLR, pyruvate kinase, liver and RBC; RPL5, ribosomal protein L5; RPS29, ribosomal protein S29; RUNX1, runt related transcription factor 1; SPTB, spectrin beta, erythrocytic; UGT1A1, UDP glucuronosyltransferase family 1 member A1. *, Stop codon. †, novel mutation in compound heterozygous cases.