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Diagnosis and Treatment > Investigation > Western blotting

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Jasmeet Kaur Division of Biomedical Science, Department of Biochemistry, Mercer University School of Medicine and Memorial University Medical Center, Hoskins Research Building, 4700 Waters Avenue, Savannah, Georgia, 31404, USA

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Luis Casas Division of Endocrinology, Department of Pediatrics, University of North Dakota, Fargo, North Dakota, USA

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Himangshu S Bose Division of Biomedical Science, Department of Biochemistry, Mercer University School of Medicine and Memorial University Medical Center, Hoskins Research Building, 4700 Waters Avenue, Savannah, Georgia, 31404, USA
Anderson Cancer Institute, Memorial University Medical Center, Savannah, Georgia, 31404, USA

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Summary

Lipoid congenital adrenal hyperplasia (lipoid CAH), the most severe form of CAH, is most commonly caused by mutations in steroidogenic acute regulatory protein (STAR), which is required for the movement of cholesterol from the outer to the inner mitochondrial membranes to synthesize pregnenolone. This study was performed to evaluate whether the salt-losing crisis and the adrenal inactivity experienced by a Scandinavian infant is due to a de novo STAR mutation. The study was conducted at the University of North Dakota, the Mercer University School of Medicine and the Memorial University Medical Center to identify the cause of this disease. The patient was admitted to a pediatric endocrinologist at the Sanford Health Center for salt-losing crisis and possible adrenal failure. Lipoid CAH is an autosomal recessive disease, we identified two de novo heterozygous mutations (STAR c.444C>A (STAR p.N148K) and STAR c.557C>T (STAR p.R193X)) in the STAR gene, causing lipoid CAH. New onset lipoid CAH can occur through de novo mutations and is not restricted to any specific region of the world. This Scandinavian family was of Norwegian descent and had lipoid CAH due to a mutation in S TAR exons 4 and 5. Overexpression of the STAR p.N148K mutant in nonsteroidogenic COS-1 cells supplemented with an electron transport system showed activity similar to the background level, which was ∼10% of that observed with wild-type (WT) STAR. Protein-folding analysis showed that the finger printing of the STAR p.N148K mutant is also different from the WT protein. Inherited STAR mutations may be more prevalent in some geographical areas but not necessarily restricted to those regions.

Learning points

  • STAR mutations cause lipoid CAH.

  • This is a pure population from a caucasian family.

  • Mutation ablated STAR activity.

  • The mutation resulted in loosely folded conformation of STAR.

Taxonomy:
Clinical Overview, Gland/Organ, Adrenal, Topic, Adrenal, Hormone, ACTH, Cortisol, Hydroxypregnenolone, Pregnenolone, Progesterone, Renin, Condition/ Syndrome, Adrenal salt-wasting crisis, Congenital adrenal hyperplasia, Patient Demographics, Age, Paediatric, Gender, Female, Ethnicity, Other, Country of Treatment, United States, Diagnosis and Treatment, Signs and Symptoms, Dehydration, Hyperpigmentation, Salt wasting, Investigation, ACTH, Chromatography, Cortisol, DNA sequencing, Hydroxypregnenolone, Liquid chromatography-mass spectrometry, Molecular genetic analysis, Potassium, Pregnenolone, Progesterone, Protein fingerprinting, Protein folding analysis, Renin (blood), Sodium, Ultrasound scan, Western blotting, Intervention, Gonadectomy, Medication, Fludrocortisone, Glucocorticoids, Hydrocortisone, Mineralocorticoids, Publication Details, Case Report Type, Insight into disease pathogenesis or mechanism of therapy
DOI:
https://doi.org/10.1530/EDM-15-0119
Volume/Issue:
Volume 2016: Issue 1
Open access