Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG)

被引：2

作者：

Yang, Eu Jeen ^{[1
]}

Shim, Ye Jee ^{[2
]}

Kim, Heung Sik ^{[3
]}

Lim, Young Tak ^{[1
]}

Im, Ho Joon ^{[4
]}

Koh, Kyung-Nam ^{[4
]}

Kim, Hyery ^{[4
]}

Suh, Jin Kyung ^{[5
]}

Park, Eun Sil ^{[6
]}

Lee, Na Hee ^{[7
]}

Choi, Young Bae ^{[8
]}

Hah, Jeong Ok ^{[9
]}

Lee, Jae Min ^{[10
]}

Han, Jung Woo ^{[11
]}

Lee, Jae Hee ^{[12
]}

Lee, Young-Ho ^{[13
]}

Jung, Hye Lim ^{[14
]}

Ha, Jung-Sook ^{[15
]}

Ki, Chang-Seok ^{[16
]}

机构：

[1] Pusan Natl Univ, Dept Pediat, Sch Med, Childrens Hosp, Yangsan 50612, South Korea

[2] Keimyung Univ, Dongsan Hosp, Sch Med, Dept Pediat, Daegu 42601, South Korea

[3] Keimyung Univ, Dongsan Hosp, Sch Med, Dept Pediat, Daegu 41931, South Korea

[4] Univ Ulsan, Coll Med, Dept Pediat, Asan Med Ctr,Childrens Hosp, Seoul 05505, South Korea

[5] Korea Canc Ctr Hosp, Dept Pediat, Seoul 01812, South Korea

[6] Gyeongsang Natl Univ, Coll Med, Gyeongsang Natl Univ Hosp, Dept Pediat, Jinju 52727, South Korea

[7] Cha Univ, Cha Bundang Med Ctr, Dept Pediat, Seongnam 13496, South Korea

[8] Ajou Univ, Ajou Univ Hosp, Sch Med, Dept Pediat, Suwon 16499, South Korea

[9] Daegu Fatima Hosp, Dept Pediat, Daegu 41199, South Korea

[10] Yeungnam Univ, Dept Pediat, Coll Med, Daegu 42415, South Korea

[11] Yonsei Univ, Yonsei Univ Hlth Syst, Coll Med, Dept Pediat, Seoul 03722, South Korea

[12] Chungbuk Natl Univ, Chungbuk Natl Univ Hosp, Sch Med, Dept Pediat, Cheongju 28644, South Korea

[13] Hanyang Univ, Seoul Hosp, Dept Pediat, Seoul 04763, South Korea

[14] Sungkyunkwan Univ, Sch Med, Deparment Pediat, Kangbuk Samsung Hosp, Seoul 03181, South Korea

[15] Keimyung Univ, Dongsan Hosp, Sch Med, Dept Lab Med, Daegu 42601, South Korea

[16] Green Cross Genome, Yongin 16924, South Korea

来源：

GENES | 2021年 / 12卷 / 05期

关键词：

blood platelet disorders; high-throughput nucleotide sequencing; thrombasthenia; whole exome sequencing; whole genome sequencing; MUTATIONS; SUBUNIT; BETA-3; ITGA2B; PRO;

D O I：

10.3390/genes12050693

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology Group from March 2017 to December 2020, aimed to identify the causative genetic variants of IPFDs in Korean patients using next-generation sequencing (NGS). Targeted exome sequencing, followed by whole-genome sequencing, was performed for diagnosing IPFDs. Of the 11 unrelated patients with suspected IPFDs enrolled in this study, 10 patients and 2 of their family members were diagnosed with Glanzmann thrombasthenia (GT). The variant c.1913+5G>T of ITGB3 was the most common, followed by c.2333A>C (p.Gln778Pro) of ITGB2B. Known variants of GT, including c.917A>C (p.His306Pro) of ITGB3 and c.2975del (p.Glu992Glyfs*), c.257T>C (p.Leu86Pro), and c.1750C>T (p.Arg584*) of ITGA2B, were identified. Four novel variants of GT, c.1451G>T (p.Gly484Val) and c.1595G>T (p.Cys532Phe) of ITGB3 and c.1184G>T (p.Gly395Val) and c.2390del (p.Gly797Valfs*29) of ITGA2B, were revealed. The remaining patient was diagnosed with platelet type bleeding disorder 18 and harbored two novel RASGRP2 variants, c.1479dup (p.Arg494Alafs*54) and c.813+1G>A. We demonstrated the successful application of NGS for the accurate and differential diagnosis of heterogeneous IPFDs.

引用

页数：8

共 1 条

[1] "CHildren with Inherited Platelet disorders Surveillance" (CHIPS) retrospective and prospective observational cohort study by Italian Association of Pediatric Hematology and Oncology (AIEOP)
Lassandro, Giuseppe
Palladino, Valentina
Faleschini, Michela
Barone, Angelica
Boscarol, Gianluca
Cesaro, Simone
Chiocca, Elena
Farruggia, Piero
Giona, Fiorina
Gorio, Chiara
Maggio, Angela
Marinoni, Maddalena
Marzollo, Antonio
Palumbo, Giuseppe
Russo, Giovanna
Saracco, Paola
Spinelli, Marco
Verzegnassi, Federico
Morga, Francesca
Savoia, Anna
Giordano, Paola
FRONTIERS IN PEDIATRICS, 2022, 10

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