Androgen Receptor CAG Repeat Length in Relation to Phenotype Among Females with Nonclassical 21-Hydroxylase Deficiency

S. Ben-Shachar; I. Ayalon; H. Reznik-Wolf; Y. Tenenbaum-Rakover; N. Zuckerman-Levin; O. Cohen; A. Lifshitz; M. Fraenkel; Y. Toledano; V. Rouach; I. Koren; D. Modan-Moses; D. Hirsch; A. Schachter-Davidov; S. Israel; O. Eyal; N. Weintrob

doi:10.1055/s-0034-1389901

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2015; 47(07): 491-496
DOI: 10.1055/s-0034-1389901

Endocrine Care

Androgen Receptor CAG Repeat Length in Relation to Phenotype Among Females with Nonclassical 21-Hydroxylase Deficiency

S. Ben-Shachar^*

¹Genetic Institute, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

,

I. Ayalon^*

²Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

,

H. Reznik-Wolf

³Genetic Institute, Sheba Medical Center, Tel Hashomer, Israel

,

Y. Tenenbaum-Rakover

⁴Pediatric Endocrine Unit, Ha’Emek Medical Center, Afula, Israel

⁵The Technion Faculty of Medicine, Haifa, Israel

,

N. Zuckerman-Levin

⁵The Technion Faculty of Medicine, Haifa, Israel

⁶Pediatric Diabetes Unit, Meyer Children’s Hospital, Haifa, Israel

,

O. Cohen

⁷Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Israel

⁸Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

,

A. Lifshitz

⁹Endocrinology, Kupat-Holim Clalit, Israel

,

M. Fraenkel

¹⁰Endocrine Unit, Soroka Medical Center, and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

,

Y. Toledano

¹¹Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva, Israel

,

V. Rouach

¹²Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

,

I. Koren

¹³Pediatric Endocrinology Clinic, Armon Child Center, Clalit HMO, Haifa, Israel

,

D. Modan-Moses

⁸Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

¹⁴Pediatric Endocrinology and Diabetes Unit, The Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Israel

,

D. Hirsch

⁸Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

¹⁵Institute for Endocrinology and Diabetes, Rabin Medical Center, Petah Tikva, Israel

,

A. Schachter-Davidov

²Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

,

S. Israel

¹⁶Tissue Typing Unit, Hadassah University Hospital, Jerusalem, Israel

,

O. Eyal^§

²Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

⁸Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

,

N. Weintrob^§

²Pediatric Endocrinology and Diabetes Unit, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel

⁸Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

› Author Affiliations

Abstract

Nonclassical 21-hydroxylase deficiency (NC21OHD) manifests with various degrees of post natal virilization. The length of CAG repeats of the androgen receptor gene (AR) is inversely correlated to activity of the human androgen receptor (AR) and affects phenotype of several androgen-dependent disorders. The aim of the study was to investigate the associations between CAG repeat length and the phenotype of females with NC21OHD. CAG repeat length and AR inactivation were assessed in females with NC21OHD, and related to their clinical presentation. CAG repeat length and AR inactivation were assessed in 119 females with NC21OHD. Biallelic mean (BAM) of the CAG repeat length and the weighted BAM (WBAM) were related to various clinical parameters. Age at diagnosis and age of menarche positively correlated with BAM (r=0.22, p=0.02, and r=0.23, p=0.01, respectively). A shorter (<25) BAM was associated with younger age at diagnosis (14.8 vs. 21.4 years, p<0.01), at adrenarche (8.1 vs. 10.2 years, p<0.01) and gonadarche (9.9 vs. 11.2 years, p<0.01), and higher corrected height standard deviation score at diagnosis (0.77 vs. 0.15, p=0.01). Precocious pubarche and precocious puberty were more frequent in these with the shorter BAM. Results of WBAM were similar. The CAG repeat length of the AR gene contributes to the clinical diversity of the phenotype in females with NC21OHD.

Key words

congenital adrenal hyperplasia - NC21OHD - AR

Full Text

References

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