Abstract
Cultured lymphoblastoid cells of a patient with B_1 responsive lactic acidemia were found to show reduced activity of pyruvate dehydrogenase (E_1) complex and E_1, decreased affinity of E_1 for thiamine pyrophosphate and defective activation of E_1 complex by E_1 phosphatase. A single A to G transition was identified at position 131 of E_<1α>-subunit cDNA, resulting in the substitution of Arg-44 for His-44. This mutation seemed to cause a conformational change of the E_<1α>-subunit, resulting in multiple dysfunctions of E_1 in the patient. In the patients with D-dependent rickets type II, their fibroblasts displayed normal cytosol binding and impaired nuclear uptake of 1,25-dihydroxy D_3. A unique G to A transition at position 140 in exon 3 of the D receptor cDNA, resulting in the substitution of Arg-47 by Gln-47 was revealed. The Arg-47 is located in the DNA-binding domain and is conserved within all steroid hormone receptor. Therefore, it is highly conceivable that this amino acid substitution is responsible for the defect of the D receptor in the patients.
