This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bose, H. S. Articles by Miller, W. L. Search for Related Content PubMed PubMed Citation Articles by Bose, H. S. Articles by Miller, W. L.

Mutations in the Steroidogenic Acute Regulatory Protein (StAR) in Six Patients with Congenital Lipoid Adrenal Hyperplasia¹

Department of Pediatrics and Metabolic Research Unit, University of California (H.S.B., W.L.M.), San Francisco, California 94143-0978; Department of Pediatrics, Keio University Medical School (S.S., N.M.), Tokyo 160, Japan; Hackensack University Medical Center (J.A.), Hackensack, New Jersey 07601; and Ha’Emek Medical Center (S.A.S.), Afula 18101, Israel

Address all correspondence and requests for reprints to: Prof. Walter L. Miller, Department of Pediatrics, Building MR IV, Room 205, University of California, San Francisco, California 94143-0978.

Congenital lipoid adrenal hyperplasia (lipoid CAH), the most severe form of CAH, is caused by mutations in the steroidogenic acute regulatory protein (StAR). Lipoid CAH is common among the Japanese, Korean, and Palestinian Arab populations, but is rare elsewhere. We describe six patients with lipoid CAH: four Japanese, one Palestinian, and one Guatemalan Native American. All had classical clinical presentations of normal female external genitalia in both genetic sexes, with severe glucocorticoid and mineralocorticoid deficiency presenting in the first month of life. Quite atypically, one patient had small adrenal glands shown by computed tomographic scanning. The StAR genes were characterized in all six patients. Three of the Japanese patients were compound heterozygotes for the common Japanese mutation Q258X in association with three different novel frameshift mutations; the fourth Japanese patient was homozygous for the mutation R182L, which is common among Palestinian patients but has not been described previously in a Japanese patient. Our Palestinian and Native American patients were each homozygous for novel frameshift mutations. Thus we have found five new frameshift mutations, but no new amino acid replacement (missense) mutations. This would be consistent with the view that only a small number of residues in the StAR protein are crucial for biological activity. The tomographic finding of small adrenals in a patient with genetically proven lipoid CAH due to a StAR mutation suggests a substantially broader spectrum of clinical findings in this disease than has been appreciated previously.

This article has been cited by other articles:

				S. Bens, A. Mohn, B. Yuksel, A. E. Kulle, M. Michalek, F. Chiarelli, M. Nuri Ozbek, I. Leuschner, J. Grotzinger, P.-M. Holterhus, et al. Congenital Lipoid Adrenal Hyperplasia: Functional Characterization of Three Novel Mutations in the STAR Gene J. Clin. Endocrinol. Metab., March 1, 2010; 95(3): 1301 - 1308. [Abstract] [Full Text] [PDF]

				P. R. Manna, I. T. Huhtaniemi, and D. M. Stocco Mechanisms of Protein Kinase C Signaling in the Modulation of 3',5'-Cyclic Adenosine Monophosphate-Mediated Steroidogenesis in Mouse Gonadal Cells Endocrinology, July 1, 2009; 150(7): 3308 - 3317. [Abstract] [Full Text] [PDF]

				G. Sasaki, T. Ishii, P. Jeyasuria, Y. Jo, A. Bahat, J. Orly, T. Hasegawa, and K. L. Parker Complex Role of the Mitochondrial Targeting Signal in the Function of Steroidogenic Acute Regulatory Protein Revealed by Bacterial Artificial Chromosome Transgenesis in Vivo Mol. Endocrinol., April 1, 2008; 22(4): 951 - 964. [Abstract] [Full Text] [PDF]

				C. J. Kim, L. Lin, N. Huang, C. A. Quigley, T. W. AvRuskin, J. C. Achermann, and W. L. Miller Severe Combined Adrenal and Gonadal Deficiency Caused by Novel Mutations in the Cholesterol Side Chain Cleavage Enzyme, P450scc J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 696 - 702. [Abstract] [Full Text] [PDF]

				M. Abdulhadi-Atwan, A. Jean, W. K. Chung, K. Meir, Z. Ben Neriah, G. Stratigopoulos, S. E. Oberfield, I. Fennoy, H. J. Hirsch, A. Bhangoo, et al. Role of a Founder c.201_202delCT Mutation and New Phenotypic Features of Congenital Lipoid Adrenal Hyperplasia in Palestinians J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 4000 - 4008. [Abstract] [Full Text] [PDF]

				M. Bose, D. Debnath, Y. Chen, and H. S Bose Folding, activity and import of steroidogenic acute regulatory protein into mitochondria changed by nicotine exposure J. Mol. Endocrinol., July 1, 2007; 39(1): 67 - 79. [Abstract] [Full Text] [PDF]

				B. Y. Baker, R. F. Epand, R. M. Epand, and W. L. Miller Cholesterol Binding Does Not Predict Activity of the Steroidogenic Acute Regulatory Protein, StAR J. Biol. Chem., April 6, 2007; 282(14): 10223 - 10232. [Abstract] [Full Text] [PDF]

				B. Y. Baker, L. Lin, C. J. Kim, J. Raza, C. P. Smith, W. L. Miller, and J. C. Achermann Nonclassic Congenital Lipoid Adrenal Hyperplasia: A New Disorder of the Steroidogenic Acute Regulatory Protein with Very Late Presentation and Normal Male Genitalia J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4781 - 4785. [Abstract] [Full Text] [PDF]

				H. Morgan, V. Battista, and S. S. Leopold Constraint in Primary Total Knee Arthroplasty J. Am. Acad. Ortho. Surg., December 1, 2005; 13(8): 515 - 524. [Abstract] [Full Text] [PDF]

				A. Bhangoo, W.-X. Gu, S. Pavlakis, H. Anhalt, L. Heier, S. Ten, and J. L. Jameson Phenotypic Features Associated with Mutations in Steroidogenic Acute Regulatory Protein J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6303 - 6309. [Abstract] [Full Text] [PDF]

				C. E. Fluck, A. Maret, D. Mallet, S. Portrat-Doyen, J. C. Achermann, B. Leheup, G. E. Theintz, P. E. Mullis, and Y. Morel A Novel Mutation L260P of the Steroidogenic Acute Regulatory Protein Gene in Three Unrelated Patients of Swiss Ancestry with Congenital Lipoid Adrenal Hyperplasia J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5304 - 5308. [Abstract] [Full Text] [PDF]

				X. Chen, B. Y. Baker, M. A. Abduljabbar, and W. L. Miller A Genetic Isolate of Congenital Lipoid Adrenal Hyperplasia with Atypical Clinical Findings J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 835 - 840. [Abstract] [Full Text] [PDF]

				Y. Jo and D. M. Stocco Regulation of Steroidogenesis and Steroidogenic Acute Regulatory Protein in R2C Cells by DAX-1 (Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X Chromosome, Gene-1) Endocrinology, December 1, 2004; 145(12): 5629 - 5637. [Abstract] [Full Text] [PDF]

				S. R. King, S. D. Ginsberg, T. Ishii, R. G. Smith, K. L. Parker, and D. J. Lamb The Steroidogenic Acute Regulatory Protein Is Expressed in Steroidogenic Cells of the Day-Old Brain Endocrinology, October 1, 2004; 145(10): 4775 - 4780. [Abstract] [Full Text] [PDF]

				A. A. Gonzalez, M. L. Reyes, C. A. Carvajal, J. A. Tobar, L. M. Mosso, P. Baquedano, A. Solar, A. Venegas, and C. E. Fardella Congenital Lipoid Adrenal Hyperplasia Caused by a Novel Splicing Mutation in the Gene for the Steroidogenic Acute Regulatory Protein J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 946 - 951. [Abstract] [Full Text] [PDF]

				T. Ishii, T. Hasegawa, C.-I Pai, N. Yvgi-Ohana, R. Timberg, L. Zhao, G. Majdic, B.-c. Chung, J. Orly, and K. L. Parker The Roles of Circulating High-Density Lipoproteins and Trophic Hormones in the Phenotype of Knockout Mice Lacking the Steroidogenic Acute Regulatory Protein Mol. Endocrinol., October 1, 2002; 16(10): 2297 - 2309. [Abstract] [Full Text] [PDF]

				S. L. Gyles, C. J. Burns, B. J. Whitehouse, D. Sugden, P. J. Marsh, S. J. Persaud, and P. M. Jones ERKs Regulate Cyclic AMP-induced Steroid Synthesis through Transcription of the Steroidogenic Acute Regulatory (StAR) Gene J. Biol. Chem., September 7, 2001; 276(37): 34888 - 34895. [Abstract] [Full Text] [PDF]