A new compound heterozygous frameshift mutation in the type II 3{beta}-hydroxysteroid dehydrogenase 3{beta}-HSD gene causes salt-wasting 3{beta}-HSD deficiency congenital adrenal hyperplasia

Zhang, L; Sakkal-Alkaddour, S; Chang, Ying T; Yang, Xiaojiang; Pang, Songya

doi:10.1210/jc.81.1.291

Title: A new compound heterozygous frameshift mutation in the type II 3{beta}-hydroxysteroid dehydrogenase 3{beta}-HSD gene causes salt-wasting 3{beta}-HSD deficiency congenital adrenal hyperplasia

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Abstract

We report a new compound heterozygous frameshift mutation in the type II 3{Beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) gene in a Pakistanian female child with the salt-wasting form of 3{Beta}-HSD deficiency congenital adrenal hyperplasia. The etiology for her congenital adrenal hyperplasia was not defined. Although the family history suggested possible 3{beta}-HSd deficiency disorder, suppressed adrenal function caused by excess glucocorticoid therapy in this child at 7 yr of age did not allow hormonal diagnosis. To confirm 3{beta}-HSD deficiency, we sequenced the type II 3{beta}-HSD gene in the patient, her family, and the parents of her deceased paternal cousins. The type II 3{beta}-HSD gene region of a putative promotor, exons I, II, III, and IV, and exon-intron boundaries were amplified by PCR and sequenced in all subjects. The DNA sequence of the child revealed a single nucleotide deletion at codon 318 [ACA(Thr){r_arrow}AA] in exon IV in one allele, and two nucleotide deletions at codon 273 [AAA(Lys){r_arrow}A] in exon IV in the other allele. The remaining gene sequences were normal. The codon 318 mutation was found in one allele from the father, brother, and parents of the deceased paternal cousins. The codon 273 mutation was found in one allele of the mother and a sister.more »« less

Authors:

Zhang, L; Sakkal-Alkaddour, S; Chang, Ying T; Yang, Xiaojiang; Pang, Songya ^[1]

Univ. of Illinois, Chicago, IL (United States)

Publication Date:: Mon Jan 01 00:00:00 EST 1996

OSTI Identifier:: 393909

Resource Type:: Journal Article

Journal Name:: Journal of Clinical Endocrinology and Metabolism

Additional Journal Information:: Journal Volume: 81; Journal Issue: 1; Other Information: PBD: Jan 1996

Country of Publication:: United States

Language:: English

Subject:: 55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; GENE MUTATIONS; DNA SEQUENCING; CHILDREN; HEREDITARY DISEASES; METABOLIC DISEASES; UROGENITAL SYSTEM DISEASES; CONGENITAL DISEASES; OXIDOREDUCTASES; ETIOLOGY; GENETICS; ADRENAL GLANDS; POLYMERASE CHAIN REACTION; AMINO ACIDS; EXONS; NUCLEOTIDES; STEROIDS

Citation Formats


                    Zhang, L, Sakkal-Alkaddour, S, Chang, Ying T, Yang, Xiaojiang, and Pang, Songya. A new compound heterozygous frameshift mutation in the type II 3{beta}-hydroxysteroid dehydrogenase 3{beta}-HSD gene causes salt-wasting 3{beta}-HSD deficiency congenital adrenal hyperplasia.  United States: N. p., 1996. 
        Web.  doi:10.1210/jc.81.1.291.

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                    Zhang, L, Sakkal-Alkaddour, S, Chang, Ying T, Yang, Xiaojiang, & Pang, Songya. A new compound heterozygous frameshift mutation in the type II 3{beta}-hydroxysteroid dehydrogenase 3{beta}-HSD gene causes salt-wasting 3{beta}-HSD deficiency congenital adrenal hyperplasia.  United States.  https://doi.org/10.1210/jc.81.1.291

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                    Zhang, L, Sakkal-Alkaddour, S, Chang, Ying T, Yang, Xiaojiang, and Pang, Songya. 1996.  
        "A new compound heterozygous frameshift mutation in the type II 3{beta}-hydroxysteroid dehydrogenase 3{beta}-HSD gene causes salt-wasting 3{beta}-HSD deficiency congenital adrenal hyperplasia".  United States.  https://doi.org/10.1210/jc.81.1.291.

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@article{osti_393909,

  title        = {A new compound heterozygous frameshift mutation in the type II 3{beta}-hydroxysteroid dehydrogenase 3{beta}-HSD gene causes salt-wasting 3{beta}-HSD deficiency congenital adrenal hyperplasia},

  author       = {Zhang, L and Sakkal-Alkaddour, S and Chang, Ying T and Yang, Xiaojiang and Pang, Songya},

  abstractNote = {We report a new compound heterozygous frameshift mutation in the type II 3{Beta}-hydroxysteroid dehydrogenase (3{beta}-HSD) gene in a Pakistanian female child with the salt-wasting form of 3{Beta}-HSD deficiency congenital adrenal hyperplasia. The etiology for her congenital adrenal hyperplasia was not defined. Although the family history suggested possible 3{beta}-HSd deficiency disorder, suppressed adrenal function caused by excess glucocorticoid therapy in this child at 7 yr of age did not allow hormonal diagnosis. To confirm 3{beta}-HSD deficiency, we sequenced the type II 3{beta}-HSD gene in the patient, her family, and the parents of her deceased paternal cousins. The type II 3{beta}-HSD gene region of a putative promotor, exons I, II, III, and IV, and exon-intron boundaries were amplified by PCR and sequenced in all subjects. The DNA sequence of the child revealed a single nucleotide deletion at codon 318 [ACA(Thr){r_arrow}AA] in exon IV in one allele, and two nucleotide deletions at codon 273 [AAA(Lys){r_arrow}A] in exon IV in the other allele. The remaining gene sequences were normal. The codon 318 mutation was found in one allele from the father, brother, and parents of the deceased paternal cousins. The codon 273 mutation was found in one allele of the mother and a sister. These findings confirmed inherited 3{beta}-HSD deficiency in the child caused by the compound heterozygous type II 3{beta}-HSD gene mutation. Both codons at codons 279 and 367, respectively, are predicted to result in an altered and truncated type II 3{beta}-HSD protein, thereby causing salt-wasting 3{beta}-HSD deficiency in the patient. 21 refs., 2 figs., 1 tab.},

  doi          = {10.1210/jc.81.1.291},

  url          = {https://www.osti.gov/biblio/393909},
  journal      = {Journal of Clinical Endocrinology and Metabolism},
number       = 1,

  volume       = 81,

  place        = {United States},

  year         = {Mon Jan 01 00:00:00 EST 1996},

  month        = {Mon Jan 01 00:00:00 EST 1996}

}

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