Amyotrophic onset in GCH1 dopa-responsive dystonia

Dopa-responsive dystonia (DRD) belongs to combined dystonia syndrome (dystonia-plus syndrome)1 which encompasses non-degenerative and neurometabolic disorders characterized by combination of dystonia as the prominent sign, with another movement manifestation. Parkinsonism and myoclonus are the main disturbances accompany dystonia in the combined dystonia syndrome. Dystonia with parkinsonism includes DRD [DYT5, tyrosine hydroxylase (TH), and sepiapterin reductase (SPR)], dopamine agonist-responsive dystonia, rapid-onset dystonia parkinsonism (DYT12), and early-onset dystonia with parkinsonism (DYT16). However, dystonia combined with myoclonus is just classified as myoclonus dystonia (DYT11).2 DRD can be inherited in either autosomal dominant or autosomal recessive patterns. The autosomal dominant inheritance results in the typical phenotype of DRD, known as DYT5 or Segawa disease, which is caused by heterozygous mutations of guanosine triphosphate (GTP) cyclohydrolase I gene (GCH1). Mutations of the TH and SPR genes are responsible for autosomal recessive types of DRD.3 DYT5 is represented as progressive lower limbs dystonia with childhood-onset at the common age of 2-5 years. It shows diurnal fluctuations, which are aggravated toward the evening and alleviated by sleeping. Excellent and sustained response to the low dose of levodopa is the marked feature of DYT5 disease. Additional parkinsonism and spasticity may present later in life.4 Moreover, hemiatrophy of the brain, body, or both has been reported in patients with DRD, associated with a biochemical lesion located in basal ganglia.5 However, focal atrophy and muscle weakness rarely accompanies DRD. Interestingly, we aimed to introduce weakness and focal muscle atrophy as the onset manifestations of DRD in an elderly man misdiagnosed for about 70 years.

Sugary enhancer1 (se1) Gene Endosperm Dosage and Sweet Corn Carbohydrate Content

Inbreds IL451b sugary1 (su1) and IL678a su1 isogenic for the sugary enhancer1 (se1) gene mutation were used to analyze the relationship between se1 gene dosage and endosperm sugar content. Each line was self-pollinated and reciprocal crosses were made between the isolines of each genotype to produce se1 gene dosages of 0, 1, 2, and 3 in the triploid endosperm. Ears were harvested at 15, 18, 21, 24, 27, and 45 days after pollination (DAP). Whole kernels were freeze-dried, ground into powder, and stored at –80°C until subsequent chemical analyses. Sucrose, glucose and fructose were analyzed using high-pressure liquid chromatography (HPLC), the results of which indicated a significant increase in kernel sugar content when the se1 allele is homozygous. \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[\begin{array}{lcl}&\underline{\mathrm{Sucrose\ content\ at}{\ }21{\ }\mathrm{DAP}(\%{\ }\mathrm{dry}{\ }\mathrm{wt})}&\\\underline{se1{\ }\mathrm{dose}}&\underline{\mathrm{IL}{\ }451\mathrm{b}}&\underline{\mathrm{IL}{\ }678\mathrm{a}}\\0&9.6&10.3\\1&8.0&10.7\\2&11.3&10.9\\3&15.8&12.2\end{array}\] \end{document} Sucrose content at 21 DAP (typical maturity for harvesting) was observed to increase in the IL451b and IL678a backgrounds from zero to three doses of se1 by 65% and 18% respectively, indicating that this mutation varies in its expression in different genetic backgrounds. Associations between kernel phytoglycogen and starch content and se1 gene dosage are presented. The biochemical lesion associated with the se1 gene product is discussed.

Bone marrow cells from vitamin B12- and folate-deficient patients misincorporate uracil into DNA

Bone marrow cells from 15 patients with normal deoxyuridine (dU) suppression test results, 3 healthy subjects, and 11 patients with megaloblastic anemia caused by vitamin B12 or folate deficiency were examined for misincorporation of uracil into DNA. Cells were incubated with [5–3H] uridine for 2 hours and their DNA extracted. The DNA was hydrolyzed to deoxyribonucleosides with DNase 1, phosphodiesterase and alkaline phosphatase, and any dU present was separated from other deoxyribonucleosides by Aminex A6 chromatography. The quantity of dU/mg DNA and the radioactivity in the dU peak/mg DNA were then calculated. The results clearly showed that there was markedly increased uracil misincorporation into the DNA of vitamin B12- or folate-deficient marrow cells. Misincorporation of uracil into DNA may be an important biochemical lesion underlying both the megaloblastic change and the ineffectiveness of hematopoiesis in vitamin B12 and folate deficiency.