Margaret Patterson

PCR‐based diagnosis of the Filipino (−−FIL) and Thai (−−THAI) α‐thalassemia‐1 deletions

In southeast Asia, the carrier frequency of two‐gene α‐thalassemia deletions is quite high, ranging from 4% to 14% depending on the population. The most common α‐thalassemia‐1 deletion is the so‐called southeast Asian deletion (−−SEA). In addition, a significant proportion of cases involve two other deletions, the Filipino (−−FIL) and Thai (−−THAI) deletions. In this report, we identify the deletion breakpoints for the (−−FIL) and (−−THAI) deletions, and describe PCR‐based protocols for rapid and reliable DNA diagnosis of these deletions. Am. J. Hematol. 63:54–56, 2000.

De novo mutation of the β‐globin gene initiation codon (ATG→AAG) in a Northern European

We present a case of β‐thalassemia intermedia involving a 13‐year‐old boy of Northern European descent. His mother, father and older sister have normal hematologic indices. Molecular studies demonstrate that the proband carries a novel mutation of the β‐globin gene initiation codon (ATG→AAG) which should give rise to β°‐thalassemia trait. The possibility of non‐paternity was excluded, indicating that the novel mutation was the result of a de novo event. A review of the literature indicates that mutations involving the β‐globin gene initiation codon can give rise to a more severe phenotype than is generally associated with most other β+ or β° mutations. Am. J. Hematol. 56:179–182, 1997.

Spectrum of beta-thalassemia mutations in Egypt.

Carrier screening and prenatal diagnosis programs have successfully reduced the incidence of β-thalassemia (thal) in countries where the carrier rates are high (1-3). The incidence of β-thal is particularly high in Egypt (4) due to the combined effects of high carrier rates (5) and consanguineous marriages (6). As a prerequisite to establishing effective programs for prenatal diagnosis, it is important to identify the spectrum of mutations within the population. To this end, we have surveyed the β-thal mutations for a cohort of 55 transfusion-dependent β-thal patients from the Alexandria region of Egypt and the adjacent rural governorates. Affected siblings were not included in the study. The patients were either Moslem (46/55, 84%) or Christian (9/55, 16%). Almost three-quarters (40/55, 73%) of the patients had consanguineous parents.

β-thalassemia intermedia in a Lebanese child due to homozygosity for the -88 (C→T) mutation

We report a case of beta-thalassemia intermedia involving a 3-year-old male child of Lebanese descent. Molecular studies of the family showed that he is homozygous for the -88 (C-->T) beta (+)-thalassemia mutation. This mutation is the second most common cause of beta-thalassemia in Black populations, and has also been reported in Asian Indians. A review of Lebanese beta-thalassemia cases revealed considerable mutation heterogeneity and excess homozygosity due to consanguinity.

Identifican of A New High Oxygen Affinity Hemoglobin Variant: Hb Aurora [β139(H17)Asn→Tyr]

A 73-year-old female of Dutch descent was referred for investigation of a high oxygen affinity hemoglobin variant. The β-globin gene was amplified using the polymerase chain reaction. Direct nucleotide sequencing of the polymerase chain reaction amplified DNA revealed that she is heterozygous for a novel p-globin gene mutation at codon 139, AAT→TAT. The resulting hemoglobin variant has been designated Hb Aurora [β139 (H17) Asn→Tyr].