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Войти в исследования Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics · 2026
[Phenotypic modification of β-Thalassemia by variants of SUPT5H gene: Report of two pedigrees and a literature review].
СтатьяОбзорКлинический случайАннотация на английскомНазвание и аннотация: Перевод в очереди
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Huang Xiangyuan, Zhong Lijuan, Zhang Rui
Аннотация
OBJECTIVE: To investigate the genetic and clinical characteristics of two Chinese pedigrees exhibiting β-thalassemia traits due to variants of SUPT5H gene and conduct a literature review.
METHODS: Two pregnant women and their family members with abnormal thalassemia screening results were selected as study subjects. Clinical data were collected, and peripheral blood DNA was extracted for thalassemia-targeted gene testing and whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Pathogenicity of the candidate variants were rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). A literature review was also carried out on SUPT5H variants associated with thalassemia by searching the PubMed database. This study was approved by the Ethics Committee of Bao'an Women's and Children's Hospital [Ethics No.: LLSC-2025-02-05-15-KS].
RESULTS: Both probands exhibited mild anemia during pregnancy, which was characterized by typical hypochromic microcytic anemia, while no pathogenic variant was detected in the HBB gene. WES and Sanger validation of family members revealed two nonsense variants (SUPT5H: c.1195C>T, p.Gln399*) and (SUPT5H: c.397C>T, p.Arg133*) in the two pedigrees. Carriers from both pedigrees exhibited elevated hemoglobin A2 (Hb A2) and reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Literature review has identified 68 cases of SUPT5H gene variants involving 35 types. Nearly all carriers had elevated Hb A2 levels, 85.2% (58/68) carriers showed decreased MCV or MCH, and 3 cases with concurrent HBB gene variants exhibited significantly lower hemoglobin levels.
CONCLUSION: Loss-of-function variants of the SUPT5H gene may cause β-thalassemia-like phenotypes through a haploinsufficiency mechanism. Routine screening for thalassemia modifier genes, including SUPT5H, is recommended for individuals with unexplained β-thalassemia phenotypes in high-prevalence areas to prevent the birth of children with moderate-to-severe thalassemia.
METHODS: Two pregnant women and their family members with abnormal thalassemia screening results were selected as study subjects. Clinical data were collected, and peripheral blood DNA was extracted for thalassemia-targeted gene testing and whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Pathogenicity of the candidate variants were rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). A literature review was also carried out on SUPT5H variants associated with thalassemia by searching the PubMed database. This study was approved by the Ethics Committee of Bao'an Women's and Children's Hospital [Ethics No.: LLSC-2025-02-05-15-KS].
RESULTS: Both probands exhibited mild anemia during pregnancy, which was characterized by typical hypochromic microcytic anemia, while no pathogenic variant was detected in the HBB gene. WES and Sanger validation of family members revealed two nonsense variants (SUPT5H: c.1195C>T, p.Gln399*) and (SUPT5H: c.397C>T, p.Arg133*) in the two pedigrees. Carriers from both pedigrees exhibited elevated hemoglobin A2 (Hb A2) and reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Literature review has identified 68 cases of SUPT5H gene variants involving 35 types. Nearly all carriers had elevated Hb A2 levels, 85.2% (58/68) carriers showed decreased MCV or MCH, and 3 cases with concurrent HBB gene variants exhibited significantly lower hemoglobin levels.
CONCLUSION: Loss-of-function variants of the SUPT5H gene may cause β-thalassemia-like phenotypes through a haploinsufficiency mechanism. Routine screening for thalassemia modifier genes, including SUPT5H, is recommended for individuals with unexplained β-thalassemia phenotypes in high-prevalence areas to prevent the birth of children with moderate-to-severe thalassemia.