Prenatal diagnosis of unusual hemoglobinopathies

✍ Scribed by Kim, Jong-Hwa ;Lebo, Roger V. ;Cai, Shi-Ping ;Su, Xia ;Chung, Jae-Hyun ;Mentzer, William C. ;Golbus, Mitchell S.

• Book ID: 102701372
• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 591 KB
• Volume: 50
• Category: Article
• ISSN: 0148-7299
• DOI: 10.1002/ajmg.1320500104

✦ Synopsis

While analyzing 280 hemoglobinopathy kindreds with prescribed molecular tests, 3 unusual mutations were observed that required additional characterization. In the first case, the hypervariable region flanking the a-globin genes generated an intermediate length 8.2 kb qc-globin gene fragment on a Southeast Asian chromosome with two deleted a-globin genes. Rehybridization of the Southern blot with a-globin probe distinguished the mutation unambiguously. In the second case, restriction enzyme analysis of a PCR amplified black f3-globin gene detected a novel P-" point mutation adjacent to a promoter element. In the third case, which was uninformative with available allele specific oligonucleotides (ASOs), total genomic PCR amplification and sequencing identified a single basepair insertion in codon 36/37 of an Iranian P-globin gene that shifted the reading frame and obliterated gene activity. Developing additional regionspecific ASOs will further diminish the number of cases that must be characterized by genomic PCR sequencing. o 1994 Wiley-Liss, Inc.