, Volume 14, Issue 1, pp 160–166 | Cite as

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

  • Roberta Minari
  • Alessandra Vottero
  • Francesco Tassi
  • Isabella Viani
  • Tauro Maria Neri
  • Maria Elisabeth Street
  • Lucia Ghizzoni
  • Sergio Bernasconi
  • Davide MartoranaEmail author
Case report


OBJECTIVE: Congenital adrenal hypoplasia (CAH) is a rare disorder that can be inherited in an X-linked or autosomal recessive pattern. CAH is frequently associated with hypogonadotropic 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.385delC; p.(Leu129Cysfs*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. CONCLUSIONS: Adrenal hypoplasia typically presents as adrenal insufficiency during the first few months of life, however, not necessarily 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.

Key words

Congenital Adrenal Hypoplasia de novo mutation Gonadal mosaicism NR0B1 gene 


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Copyright information

© Hellenic Endocrine Society 2015

Authors and Affiliations

  • Roberta Minari
    • 1
  • Alessandra Vottero
    • 1
  • Francesco Tassi
    • 1
  • Isabella Viani
    • 1
  • Tauro Maria Neri
    • 2
  • Maria Elisabeth Street
    • 3
  • Lucia Ghizzoni
    • 4
  • Sergio Bernasconi
    • 1
  • Davide Martorana
    • 2
  1. 1.Departments of Clinical and Experimental MedicineUniversity of ParmaParmaItaly
  2. 2.Unit of Molecular GeneticsUniversity Hospital of ParmaParmaItaly
  3. 3.Departments of PaediatricsUniversity Hospital of ParmaParmaItaly
  4. 4.Division of Endocrinology and Metabolism, Department of Internal MedicineUniversity of TurinTurinItaly

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