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- Title
Genotype–phenotype correlation in children with hereditary spherocytosis.
- Authors
Tole, Soumitra; Dhir, Priya; Pugi, Jakob; Drury, Luke J.; Butchart, Sheila; Fantauzzi, Michelle; Langer, Jacob C.; Baker, Jillian M.; Blanchette, Victor S.; Kirby‐Allen, Melanie; Carcao, Manuel D.
- Abstract
Summary: Hereditary spherocytosis (HS) is a common inherited haemolytic anaemia attributed to disturbances in five different red cell membrane proteins. We performed a retrospective study of 166 children with HS and describe the clinical phenotype according to the genotype. In 160/166 (97%) children with HS a disease‐causing mutation was identified. Pathogenic variants in ANK1, SPTB, SLC4A1 andSPTA1 were found in 49%, 33%, 13% and 5% of patients. Children with SLC4A1‐HS had the mildest phenotype, showing the highest haemoglobin (P < 0·001), lowest reticulocyte counts (P < 0·001) and lowest unconjugated bilirubin levels (P = 0·006), and none required splenectomy in childhood (P < 0·001). Conversely, children with autosomal recessive SPTA1‐HS had the most severe clinical phenotype, with almost all patients undergoing splenectomy in early childhood. Patients with ANK1 and SPTB variants showed a similar clinical phenotype. Within each gene, variant type or location did not predict disease severity or likelihood of splenectomy. Among patients with a genetic diagnosis, 47 (29%) underwent splenectomy (23 partial; 24 total) while 57 (36%) underwent cholecystectomy. Total splenectomy led to greater improvements in haemoglobin (P = 0·02). Select use of genetic testing (especially in patients without a family history) may help predict clinical phenotype in childhood and guide family counselling.
- Subjects
MEMBRANE proteins; FAMILY counseling; HUMAN chromosome abnormality diagnosis; ERYTHROCYTES; HEMOLYTIC anemia; RECESSIVE genes; AUTOIMMUNE hemolytic anemia; CHOLECYSTITIS
- Publication
British Journal of Haematology, 2020, Vol 191, Issue 3, p486
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.16750