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Distinct genetic profile with recurrent population-specific missense variants in Korean adult atypical hemolytic uremic syndrome

 Jae Won Yun  ;  Jisu Oh  ;  Ki-O Lee  ;  Seon Ju Lee  ;  Jung Oh Kim  ;  Nam Keun Kim  ;  Jin Seok Kim  ;  Youngil Koh  ;  Sung-Soo Yoon  ;  Ho-Young Yhim  ;  Sang-Kyung Jo  ;  Yong Park  ;  Jung Eun Lee  ;  Jinny Park  ;  Jong Wook Lee  ;  Sun-Hee Kim  ;  Hee-Jin Kim  ;  Doyeun Oh 
 THROMBOSIS RESEARCH, Vol.194 : 45-53, 2020-10 
Journal Title
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Adult ; Atypical Hemolytic Uremic Syndrome* / genetics ; Complement System Proteins ; Genetic Profile ; Humans ; Republic of Korea ; Whole Exome Sequencing
Adult ; Atypical hemolytic uremic syndrome ; Genetics ; Korea ; Thrombomodulin
Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA), characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, and renal failure. In more than half of cases, genetic defects leading to overactivation of the alternative complement system have been identified. In this study, we investigated genetic defects in Korean adult patients with aHUS.

Materials and methods: Sixty-six Korean adult patients with aHUS were ascertained from the Korean TMA Registry. Genetic variants of 15 aHUS-related genes (eight core genes [CFH, CFB, CFI, CD46, C3, THBD, PLG, and DGKE] and seven candidate genes [CFP, C4BPA, and CHFR1-5]) were analyzed from exome sequencing data. Multiplex ligation-dependent probe amplification of CFH and related genes was performed to detect hybrid genes or large deletions.

Results: Thirty patients (45%) had at least one aHUS-related variant (s) in eight core genes (total 40 variant alleles). The most frequently affected gene was CFH (13/40, 32%), followed by THBD (8/40, 20%) and CD46 (7/40, 18%). The two most common variants were Asp486Tyr of THBD (N = 7) and Tyr1058His-Val1060Leu of CFH (N = 5, linked on the same allele), accounting for 30% (12/40). In seven candidate genes, 19 variants were detected. When combined, 40 patients (61%) had at least one variant in 15 core or candidate genes. No patients had anti-CFH Ab or hybrid gene/CFHR1 homozygous deletions.

Conclusions: The genetic profile of Korean adult aHUS was unique with recurrent missense variants, demonstrating ethnicity- and age-dependent differences in the genetic background of aHUS.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jin Seok(김진석) ORCID logo https://orcid.org/0000-0001-8986-8436
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