Beta-thalassemia in association with a new delta-chain hemoglobin variant [delta116(g18)Arg-->Leu]: implications for carrier screening and prenatal diagnosis.
We describe a complicated genetic counseling and prenatal diagnostic case involving an East Indian couple that had lost two consecutive pregnancies. Hemoglobinopathy screening was conducted to investigate the possibility of Hb Bart's hydrops fetalis or Hb H hydrops fetalis. The initial work-up indicated that alpha-thalassemia was not a contributing factor, with both parents being carriers of single gene deletions (-alpha(3.7)/alphaalpha). However, the Hb electrophoresis results indicated that the couple might be at risk for having children with Hb E/Hb Lepore disease. Subsequent DNA testing demonstrated that the father carried the Hb E mutation, but failed to confirm that the mother carries the Hb Lepore deletion. Sequence analysis revealed that the mother was heterozygous for a common East Indian beta(0)-thalassemia mutation, yet had a normal level of Hb A(2). The mother also carried a previously unreported missense mutation of the delta-globin gene, in cis with the beta(0)-thalassemia mutation, which gave rise to the minor Hb variant originally misidentified as Hb Lepore. This case illustrates the importance of comprehensive molecular analyses for accurate assessment of genetic risks for hemoglobinopathy syndromes.
Hamilton Regional Laboratory Medicine Program, McMaster University Medical Centre, Hamilton, Ontario, Canada. wayej@mcmail.mcmaster.ca
John S
JS
Waye
Margaret
M
Patterson
Lynda
L
Walker
Barry
B
Eng
Lisa M
LM
Nakamura
John D
JD
Lafferty
Siu-Li
SL
Yong
John K
JK
Wu
David H K
DH
Chui
Sui-Li
SL
Yong
D000022:Abortion, Spontaneous; D000328:Adult; D004252:DNA Mutational Analysis; D003951:Diagnostic Errors; D005192:Family Health; D005260:Female; D006580:Genetic Carrier Screening; D014644:Genetic Variation; D006446:Hemoglobin E; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D007194:India / Q000208:ethnology; D008297:Male; D020125:Mutation, Missense; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic; D011296:Prenatal Diagnosis; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D006446:Hemoglobin E; C037659:hemoglobin Lepore