Congenital adrenal hypoplasia, an X-linked disorder, is characterized by primary adrenal insufficiency and frequent association with hypogonadotropic hypogonadism. The X-chromosome gene DAX-1 has been most recently identified and shown to be responsible for this disorder. We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism by using PCR amplification of genomic DNA and its complete exonic sequencing. In a family containing several affected individuals, the proband male patient had a stop codon (TGA) in place of tryptophan (TGG) at amino acid position 171. As expected, his mother was a heterozygous carrier for the mutation, whereas his father and unaffected brother did not carry this mutation. In another male patient with noncontributory family history, sequencing revealed a 1-bp (T) deletion at amino acid position 280, leading to a frame shift and, subsequently a premature stop codon at amino acid position 371. The presence of this mutation in the patients' genome was further confirmed by digestion of genomic PCR product with MspI created by this mutation. Family studies using MspI digestion of genomic PCR products revealed that neither parent of this individual carried the mutation. These results clearly indicate that congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not only inherited but also de novo mutation in the DAX-1 gene.

The pathogenesis of granulopoietic failure in systemic lupus erythematosus (SLE) was studied. In 16 Japanese women with SLE, a decreased number of granulocyte/monocyte progenitor cells (CFU‐C) in the bone marrow was demonstrated, and the number of CFU‐C correlated significantly with the peripheral blood granulocyte/monocyte count. The peripheral and bone marrow T lymphocytes suppressed the colony formation of autologous or allogeneic bone marrow CFU‐C. These findings suggest that the decreased marrow CFU‐C may be due to suppression by T lymphocytes, an event that may play an important role in the pathogenesis of granulopoietic failure in SLE.

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