Phenotypic Features Associated with Mutations in Steroidogenic Acute Regulatory Protein

Context: Mutations in the gene encoding steroidogenic acute regulatory protein (StAR) are the most common cause of lipoid congenital adrenal hyperplasia (lipoid CAH), a disorder characterized by adrenal insufficiency and deficient gonadal steroid synthesis, resulting in female external genitalia in...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 2005-11, Vol.90 (11), p.6303-6309
Main Authors: Bhangoo, Amrit, Gu, Wen-Xia, Pavlakis, Steven, Anhalt, Henry, Heier, Linda, Ten, Svetlana, Jameson, J. Larry
Format: Article
Language:English
Subjects:
Adrenal Hyperplasia, Congenital - genetics
Adrenal Hyperplasia, Congenital - pathology
Biological and medical sciences
Brain - pathology
Endocrinopathies
Female
Fundamental and applied biological sciences. Psychology
Humans
Infant
Magnetic Resonance Imaging
Medical sciences
Mutation
Phenotype
Phosphoproteins - genetics
Vertebrates: endocrinology
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Summary:Context: Mutations in the gene encoding steroidogenic acute regulatory protein (StAR) are the most common cause of lipoid congenital adrenal hyperplasia (lipoid CAH), a disorder characterized by adrenal insufficiency and deficient gonadal steroid synthesis, resulting in female external genitalia in both genetic sexes. Objective: We describe three new cases of lipoid CAH caused by novel mutations in the StAR gene. Patients: An XY subject of Yemeni descent presented with adrenal insufficiency and severe undervirilization. Magnetic resonance imaging (MRI) of the brain showed enlarged subarachnoid spaces consistent with frontal and temporal atrophy. Two XX siblings of Palestinian descent presented with neonatal adrenal insufficiency. One had a borderline intelligence quotient and features of attention deficit hyperactivity disorder. MRI showed areas of supratentorial white matter lesions. In her sister, MRI revealed a Chiari-I malformation. Results: The XY subject was found to have a missense mutation (R182C). Both XX siblings had a dinucleotide deletion at nucleotides 327–328 that induces a frame shift that truncates the StAR protein after 68 amino acids. Conclusions: These cases broaden the spectrum of known StAR mutations and suggest that disorders of central nervous system development may arise because of StAR deficiency and/or the metabolic consequences of neonatal adrenal deficiency.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.2005-0434