Phumin Chaweephisal1, Arunee Phusua1, Kanda Fanhchaksai1, Supatra Sirichotiyakul2, Pimlak Charoenkwan3. 1. Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. 2. Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. 3. Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. Electronic address: pimlak.c@cmu.ac.th.
Abstract
INTRODUCTION: Identification of beta-thalassemia carrier in prenatal screening relies on the elevated Hb A2 level. Borderline Hb A2 levels pose a diagnostic challenge. We determined the HBB genotypes in subjects with borderline Hb A2 in northern Thailand and studied the effects of coinherited alpha0-thalassemia on Hb A2 levels. METHODS: Blood samples with Hb A2 3.1-10.0% from 2193 samples submitted for prenatal thalassemia screening were selected. Information on HBB genotypes and coinherited alpha0-thalassemia were collected. All samples with unknown HBB genotypes underwent an automated DNA sequencing. The Hb A2 levels were compared according to the coinherited alpha0-thalassemia. RESULTS: HBB mutations were found in 298 (98.7%) of 302 samples with Hb A2 4.0-10.0%. In the 106 samples with Hb A2 3.1-3.9%, six had HBB mutations; four Hb Dhonburi [codon 126 (T > G)], one CAP site mutation [CAP + 1 (A > C)] and one beta0-thalassemia [codon 41/42 (-TTCT)] with a coinherited HBD mutation [nt-77 (T > C)]. The Hb A2 levels in beta-thalassemia carriers with and without coinherited alpha0-thalassemia were not significantly different. CONCLUSIONS: HBB mutations in northern Thais with borderline Hb A2 levels comprise an unstable variant Hb Dhonburi and CAP + 1 (A > C) mutation. Coinherited HBD mutation lowers Hb A2 and can cause a misidentification of a beta-thalassemia carrier.
INTRODUCTION: Identification of beta-thalassemia carrier in prenatal screening relies on the elevated Hb A2 level. Borderline Hb A2 levels pose a diagnostic challenge. We determined the HBB genotypes in subjects with borderline Hb A2 in northern Thailand and studied the effects of coinherited alpha0-thalassemia on Hb A2 levels. METHODS: Blood samples with Hb A2 3.1-10.0% from 2193 samples submitted for prenatal thalassemia screening were selected. Information on HBB genotypes and coinherited alpha0-thalassemia were collected. All samples with unknown HBB genotypes underwent an automated DNA sequencing. The Hb A2 levels were compared according to the coinherited alpha0-thalassemia. RESULTS:HBB mutations were found in 298 (98.7%) of 302 samples with Hb A2 4.0-10.0%. In the 106 samples with Hb A2 3.1-3.9%, six had HBB mutations; four Hb Dhonburi [codon 126 (T > G)], one CAP site mutation [CAP + 1 (A > C)] and one beta0-thalassemia [codon 41/42 (-TTCT)] with a coinherited HBD mutation [nt-77 (T > C)]. The Hb A2 levels in beta-thalassemia carriers with and without coinherited alpha0-thalassemia were not significantly different. CONCLUSIONS:HBB mutations in northern Thais with borderline Hb A2 levels comprise an unstable variant Hb Dhonburi and CAP + 1 (A > C) mutation. Coinherited HBD mutation lowers Hb A2 and can cause a misidentification of a beta-thalassemia carrier.