Genetic diagnosis and pathogenic analysis of an atypical hereditary spherocytosis combined with UGT1A1 partial deficiency: A case report

Yi,Yan; Dang,Xiqiang; Li,Yonggui; Zhao,Chenyu; Tang,Haiyan; Shi,Xiaoliu

doi:10.3892/mmr.2017.7867

Genetic diagnosis and pathogenic analysis of an atypical hereditary spherocytosis combined with UGT1A1 partial deficiency: A case report

Authors:
- Yan Yi
- Xiqiang Dang
- Yonggui Li
- Chenyu Zhao
- Haiyan Tang
- Xiaoliu Shi
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Affiliations: Department of Haematology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Pediatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China, Department of Medical Genetics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
Published online on: October 25, 2017 https://doi.org/10.3892/mmr.2017.7867
Pages: 382-387

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Abstract

Patients with combined hereditary spherocytosis (HS) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) deficiency have been reported sporadically. A discrepancy between the level of elevated serum bilirubin concentration and the degree of anemia may suggest the possibility of a coexistence of these conditions. In the present case report, a 20‑year‑old female presented with congenital jaundice and anemia, but did not present with the discrepancy between hyperbilirubinemia and anemia in the patient's childhood, and was not previously diagnosed with either HS or UGT1A1 deficiency. During a follow‑up of >10 years, the patient's hyperbilirubinemia accumulated progressively, whereas the patient's anemia became relatively mild. Upon further genetic analysis, it was determined that the patient had HS combined with UGT1A1 partial deficiency. Next generation sequencing combined with direct sequencing was used to identify a novel heterozygous mutation (c.G828T; p.Y276X) in the spectrin β gene, which is causative for HS. Sequence analysis of the patients' UGT1A1 gene revealed a compound heterozygote with c.G211A (p.G71R) and T3279G mutations, which reduced UGT1A1 activity to 30‑60% of the normal level. Genetic analysis was crucial for determining the diagnosis and pathogenesis of this unusual case.

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