A novel mutation in the NR0B1 gene in a family with monozygotic twin sisters and congenital adrenal hypoplasia affected children

作者：Minari Roberta; Vottero Alessandra; Tassi Francesco; Viani Isabella; Neri Tauro Maria; Street Maria Elisabeth; Ghizzoni Lucia; Bernasconi Sergio; Martorana Davide^*

来源：Hormones-International Journal of Endocrinology and Metabolism, 2015, 14(1): 160-166.

• Congenital Adrenal Hypoplasia
• de novo mutation
• Gonadal mosaicism
• NR0B1 gene

OBJECTIVE Congenital adrenal hypoplasia (CAH) is a rare, disorder that can be inherited in an X-linked or antosomal recessive pattern: CAH is frequently associated with hypogonado-tropic hypogonadism(HHG) with absent or arrested puberty and impaired fertility caused by abnormalities, in spermatogenesis. It is estimated that more than 50% of boys with idiopathic adrenal insufficiency have mutations in the NR0B1 gene product, DAX1.CASE REPORT: The proband is a young boy born after an uneventful pregnancy and delivery to non-consanguineous parents. At age 4 years and 4 months he came to our attention because of severe vomiting, abdominal pain, dehydration, and asthenia The proband underwent a detailed clinical investigation including genetic testing. Sequencing analysis of the NR0B1 gene coding region from the affected Child revealed a novel hemizygous deletion [c.385deIC; p.(Len-129Cysfs*135). This mutation was also present in the heterozygous healthy mother and in her twin sister and in the first cousin of the proband. Monozygosity of the twin sisters was demonstrated. This suggests a de novo mutation and gonadal mosaicism for the deletion. CONCLUSION: Adrenal hypoplasia typically presents as adrenal insufficiency during the first few months of life, however, not necesssarily as shown by our index case. HHG is thought to affect all NR0B1 mutated patients who reach puberty and, as understanding of the disease has improved, more of these patients survive while presenting different features of the disease, this emphasizing the value of genetic testing in boys with primary adrenal insufficiency and suspected X-linked CAH.

• 出版日期2015-3