Theodore F. Thurmon

Association of IL-13, RANTES, and leukotriene C4 synthase gene promoter polymorphisms with asthma and/or atopy in African Americans.

Purpose: IL-13, RANTES (Regulated on Activation, Normal T cells Expressed and Secreted), and cysteinyl leukotrienes are asthma and atopy mediators. Two RANTES −403(G to A) and −28(C to G), an −1055 IL-13(C to T), and a −444(A to C) leukotriene C4 synthase (LTC4S) single nucleotide polymorphisms (SNPs) have been shown in Caucasians and Asians as asthma and atopy risk factors. We studied these SNPs in African Americans with asthma and/or atopy.Methods: We studied 61 patients with asthma and/or atopy and 129 to 157 newborn controls for the −403 RANTES, −28 RANTES, and −1055 IL-13 SNPs, as well as 47 patients and 60 newborn controls for the −444 LTC4S SNP.Results: The two groups did not significantly differ at the genotypes of the −403 and −28 RANTES SNP. On the other hand, the mutant TT genotype for the −1055 IL-13 SNP was detected in 19.7% of patients versus 12.7% in controls (P < 0.04, OR 2.9, 95% CI 1.0–8.0), and the mutant T allele in 58.3% versus 36.6% in controls (P < 0.02, OR 2.4, 95% CI 1.1–5.2). In a similar fashion, for the −444 LTC4S SNP, the mutant AC genotype was detected in 19.1% versus 10.0% in controls (P > 0.28); mutant C allele had an OR of 2.1 (95% CI 0.7–6.3).Conclusion: African American asthmatics/atopics had higher frequency of the TT mutant gene for the −1055 IL-13 SNP and of its mutant T allele. Regarding the −444 LTC4S SNP, there was a definite difference, although not statistically significant, with an OR of 2.1 for the mutant AC genotype in patients. If these findings become reproduced by larger studies, it may suggest that IL-13 and LTC4S SNPs can be used as predictive markers for asthma/atopy in African Americans.

Silent hemoglobin alpha genes in apes: potential source of thalassemia.

Small quantities of unusual hemoglobins were found in 1 of 37 chimpanzees and 2 of 6 gorillas. In each genus these hemoglobins contain unique α chains that differ from the ordinary by eight to nine scattered amino acid changes. The unusual chains arise from a hitherto undetected hemoglobin 3α locus. No 3α products are found in most apes; accordingly, 3α is considered synthetically inactive in all but a few reversion mutants. Indirect evidence that the inactive 3α locus is juxtaposed to an active α locus together with the supposition that 3α exists in man provides a setting wherein thalassemia might be produced by nonhomologous recombination between two loci.

Genetic anticipation in a large family with pure autosomal dominant hereditary spastic paraplegia.

We have reinvestigated a large kindred identified over 25 years ago segregating for a form of pure autosomal dominant hereditary spastic paraplegia (HSP). We have examined additional relatives in order to refine the clinical and genetic characteristics of this disorder, and performed an analysis to determine if anticipation is present in this family. Analysis of onset ages in parent-to-child transmissions of HSP is consistent with anticipation. These results provide support for dynamic mutation as the underlying mechanism of this form of HSP, and suggest a trinucleotide repeat instability occurring primarily in the female germ line.

Nutritional Disorders among Workers in North China during National Turmoil

Previously undescribed disorders of nutrition of thiamin, niacin and pyridoxin were observed among the poor people of North China during periods of prolonged deprivation. These disorders were often elicited or exacerbated by physical exertion. Thiamin deficiency syndromes included great toe pain, heel pain, temporomandibular joint click, and painful click of the knee. Syndromes of niacin deficiency included pellagral scrotal dermatitis, hypersecretion of ear wax, and night terrors. Episodic nocturnal motor hyperfunction was caused by pyridoxin deficiency. Several cases with cardiovascular diseases were observed in which nutritional debt appeared to occur simultaneously with oxygen debt following severe physical labor. Intramuscular thiamin HCl ameliorated symptoms of impending stroke. Persons with the same symptoms who did not receive thiamin progressed to fatal stroke.

A case of insertional translocation involving chromosomes 2 and 4

We report on a 6‐year‐old Caucasian boy with direct insertion of genetic material from the short arm of chromosome 4 to the short arm of chromosome 2. He was referred for evaluation because of global developmental delay and seizure disorder. A karyotype performed at 41/2 months of age, by a laboratory elsewhere, reportedly showed a deletion of chromosome 4(p12). When we saw him, he had macrocephaly, hypotonia, psychomotor retardation, multiple minor congenital anomalies, and EEG abnormalities. Repeat chromosomes performed by our laboratory revealed that his karyotype was 46, XY, dir ins(2;4)(p24;p15.3p13).

A DELETION IN THE ANGIOTENSIN CONVERTING ENZYME (ACE)GENE IS COMMON AMONG AFRICAN AMERICANS WITH ESSENTIAL HYPERTENSION. 836

Deletion polymorphism in intron 16 of the angiotensin I-converting enzyme(ACE) gene has been found to be associated with a risk of essential hypertension in some black American populations. Among some caucasian populations, however, this same polymorphism has been found to be associated with an increased risk for myocardial infarction. In an on-going family study in black Americans, we compared the frequency of the ACE deletion polymorphism in 21 hypertensive probands with 28 normotensive healthy controls drawn from the same clinic. The frequency of the deletion allele in hypertensive probands was significantly higher than in normotensive controls, 0.738 versus 0.571 with p<0.01. This suggests that polymorphism in or near the ACE gene might contribute to an increased risk of essential hypertension in blacks.