Zunec R

Prenatal diagnosis of congenital adrenal hyperplasia (21-hydroxylase deficiency) in Croatia

We report on the prenatal diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase in 20 at-risk pregnancies (16 salt-wasting and 4 simple virilizing families). We have diagnosed 3 affected fetuses (2 males and 1 female), 3 healthy homozygotes (2 males and 1 female), and 14 healthy heterozygotes (7 females and 7 males). These data were collected over 4 years. n n n nIn 16 fetuses, the diagnosis was made with measurements of 17-hydroxyprogesterone (17-OHP) and Δ-4-androstenedione (Δ) in amniotic fluid (AF), human leukocyte antigen (HLA) typing of amniotic cells, as well as karyotypes between the 16th and 18th weeks of gestation. In 4 fetuses, DNA analysis of amniotic cells was also performed. In 3 pregnancies in which affected fetuses were suspected (on the basis of HLA typing and measurements of 17-OHP and Δ concentrations in AF), the fetuses were electively aborted between the 17th to 19th weeks of gestation by parental decision. In all aborted fetuses, diagnosis was confirmed with HLA typing, autopsy findings of hyperplastic adrenal glands, and ambiguous genitalia in female fetuses. n n n nPostnatal diagnosis was confirmed in healthy fetuses with HLA typing and serum measurements of 17-OHP concentrations, and in 4 of them with DNA analysis. In 3 of the 4 families, DNA analyses revealed the following mutations: in Family 1, the index case mutation was Intron 2, Exon 3/Exon 6, and the fetus was Normal/Exon 6; in Family 2, the index case mutation was Ex1 Int2 Ex3/Int2, and the fetus was Ex1 Int2 Ex3/Normal; and in Family 3, the index case mutation was Ex8356/Ex8356, and the fetus was Ex8356/Normal. n n n nWe also report one case of prenatal diagnosis and treatment. Dexamethasone 0.5 mg BID (20 μg/kg/d) was given starting at 6th week of gestation. Prenatal diagnosis suggested, but did not prove, that the female fetus was a heterozygote as the fetus lacked the paternal mutation Ex8318. No mutation was found in the mother. The fetus, the mother, and the affected sib shared a haplotype, further suggesting heterozygosity. The unaffected status was confirmed postnatally. Am J. Med. Genet. 72:302–306, 1997.

Human Leukocyte Antigen class II polymorphisms among Croatian patients with type 1 diabetes and autoimmune polyglandular syndrome type 3 variant

This study included 161 patients: 92 patients had type 1 diabetes (T1D) while 69 patients had a combination of T1D and autoimmune thyroiditis, the so-called autoimmune polyglandular syndrome type 3 variant (APS3v). Those patients, as well as 93 controls, were typed for HLA-DRB1 and -DQB1 genes to assess their possible contribution to the development/protection of T1D with/without autoimmune thyroiditis. Both HLA-DRB1*04 and -DRB1*03 frequencies were significantly higher among T1D and APS3v patients than in controls. The frequencies of HLA-DRB1*11 and -DRB1*15 were lower among T1D patients, while HLA-DRB1*07 and -DRB1*11 occurred significantly less frequently among APS3v patients in comparison to controls. HLA-DQB1*03:01 and -DQB1*03:02 were associated with a higher risk of developing T1D and APS3v; HLA-DQB1*02 was significantly more present among APS3v patients while HLA-DQB1*03:03 was observed with a significantly lower frequency only among T1D patients. HLA-DRB1*03~DQB1*02 and HLA-DRB1*04~DQB1*03:02 were associated with both diseases. The higher frequency of HLA-DRB1*03/DRB1*03 among APS3v patients was the only significant difference in genotype frequency when compared to T1D patients, while high risk (HLA-DRB1*03/DRB1*04) and medium risk genotypes for T1D (HLA-DRB1*04/DRB1*04) occurred with similar frequencies in both patient groups. Although some of the results point toward shared genetic susceptibility of T1D and APS3v, observed differences in both susceptible/protective HLA profiles indicate the necessity of further studies in order to elucidate the pathogenesis of these diseases.