Two novel mutations found in a patient with 17alpha-hydroxylase enzyme deficiency.

CONTEXT: Congenital adrenal hyperplasia resulting from 17alpha-hydroxylase deficiency (17OHD) is a rare disorder associated with hypertension. SUBJECT AND METHODS: We describe a phenotypically and hormonally affected female patient with 17OHD. DNA sequencing of her CYP17 gene revealed a maternal heterozygous mutation in exon 2 (R125Q) and a paternal heterozygous mutation in exon 8 (R416H). These are novel mutations in the CYP17 gene that completely eliminate enzyme activity. CONCLUSION: Identification of novel mutations in the CYP17 gene is vital in understanding the molecular mechanisms of its deficiency and in providing additional information about the structure and enzymatic functions of P450c17.

Clinical, hormonal and cytogenetic evaluation of 46,XX males and review of the literature.

The main factor influencing the sex determination of an embryo is the genetic sex determined by the presence or absence of the Y chromosome. However, some individuals carry a Y chromosome but are phenotypically female (46,XY females) or have a female karyotype but are phenotypically male (46,XX males). 46,XX maleness is a rare sex reversal syndrome affecting 1 in 20,000 newborn males. Molecular analysis of sex-reversed patients led to the discovery of the SRY gene (sex-determining region on Y). The presence of SRY causes the bipotential gonad to develop into a testis. The majority of 46, SRY-positive XX males have normal genitalia; in contrast SRY-negative XX males usually have genital ambiguity. A small number of SRY-positive XX males also present with ambiguous genitalia. Phenotypic variability observed in 46,XX sex reversed patients cannot be explained only by the presence or absence of SRY despite the fact that SRY is considered to be the major regulatory factor for testis determination. There must be some other genes either in the Y or other autosomal chromosomes involved in the definition of phenotype. In this article, we evaluate four patients with 46,XX male syndrome with various phenotypes. Two of these cases are among the first reported to be diagnosed prenatally.

Treatment with growth hormone and luteinizing hormone releasing hormone analog improves final adult height in children with congenital adrenal hyperplasia.

Final adult height is often compromised in children with congenital adrenal hyperplasia (CAH). This study examines the impact of GH and LHRH analog (LHRHa) on final adult height in patients with CAH due to 21-hydroxylase deficiency. Fourteen patients with CAH (eight males, six females) predicted to be more than 1.0 sd below their midparental target height received GH and LHRHa until final height. Each patient was matched at the start of GH therapy to a CAH patient treated only with glucocorticoids according to type of CAH, sex, and chronological age. Mean age, bone age, height, height prediction, and target height were the same in both groups at the beginning of GH therapy. Mean duration of GH treatment was 4.4 +/- 1.5 yr. Mean duration of LHRHa therapy was 4.2 +/- 2.0 yr. In the treatment group, final height sd score of -0.4 + 0.8 was significantly greater than both the initial prediction of -1.5 +/- 0.9 (P < 0.0001) and the final height sd score of the untreated group of -1.4 +/- 1.1 (P = 0.01). Our results indicate that the combination of GH and LHRHa improves final adult height in patients with CAH.