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Войти в исследования Hormone research in paediatrics · 2025
Olfactory Receptor Gene Deletions: A Novel Genetic Findings in Idiopathic Prepubertal Gynecomastia and Juvenile Macromastia.
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Bas Firdevs, Karaman Birsen, Kardelen Asli Derya, Heidargholizadeh Somayyeh, Najafli Adam, Toksoy Guven, Koc Cansu, Poyrazoglu Sukran, Yildiz Melek, Uyguner Zehra Oya, Basaran Seher, Darendeliler Feyza
Аннотация
INTRODUCTION: Prepubertal gynecomastia (PG) and juvenile macromastia (JM) are rare breast overgrowth phenotypes arising from hormonal or genetic abnormalities. While many cases reflect physiological or endocrine variation, a subset may involve increased peripheral aromatization driven by genomic factors. The molecular basis remains unknown in many idiopathic cases. We evaluated whether copy number variations (CNVs) in CYP19A1 and other estrogen-related genes are associated with PG or JM.
METHODS: We performed a cross-sectional study of 17 patients suspected of aromatase excess syndrome: 10 boys with PG and 7 girls with JM. Clinical and hormonal data at diagnosis and follow-up were reviewed. After excluding numerical and structural chromosomal anomalies, genome-wide oligonucleotide array comparative genomic hybridization (aCGH) was analyzed in Agilent Genomics Workbench (GRCh37/hg19). CNVs were interrogated across estrogen-related genes, including CYP19A1. As comparators, 988 individuals evaluated by aCGH at the same center for unrelated indications and without breast overgrowth served as controls.
RESULTS: No pathogenic CNVs were observed in CYP19A1 or the other estrogen-related genes. By contrast, a recurrent 65.2-kilobase (kb) deletion spanning the OR4P4-OR4S2-OR4C6 olfactory receptor cluster at 11q11 occurred in 40.0% (4/10) of PG and 57.1% (4/7) of JM cases, in this cohort, overall, versus 3.4% (34/988) of controls, suggesting a strong association. Estimated risk ratio was 11-fold higher in PG and 16-fold higher in JM.
CONCLUSION: Although estrogen-gene CNVs were not detected, the OR4P4-OR4S2-OR4C6 deletion may represent an under-recognized genomic contributor to idiopathic PG and JM. Prospective studies with tissue-level validation and functional assays are needed to confirm clinical significance and clarify mechanism.
METHODS: We performed a cross-sectional study of 17 patients suspected of aromatase excess syndrome: 10 boys with PG and 7 girls with JM. Clinical and hormonal data at diagnosis and follow-up were reviewed. After excluding numerical and structural chromosomal anomalies, genome-wide oligonucleotide array comparative genomic hybridization (aCGH) was analyzed in Agilent Genomics Workbench (GRCh37/hg19). CNVs were interrogated across estrogen-related genes, including CYP19A1. As comparators, 988 individuals evaluated by aCGH at the same center for unrelated indications and without breast overgrowth served as controls.
RESULTS: No pathogenic CNVs were observed in CYP19A1 or the other estrogen-related genes. By contrast, a recurrent 65.2-kilobase (kb) deletion spanning the OR4P4-OR4S2-OR4C6 olfactory receptor cluster at 11q11 occurred in 40.0% (4/10) of PG and 57.1% (4/7) of JM cases, in this cohort, overall, versus 3.4% (34/988) of controls, suggesting a strong association. Estimated risk ratio was 11-fold higher in PG and 16-fold higher in JM.
CONCLUSION: Although estrogen-gene CNVs were not detected, the OR4P4-OR4S2-OR4C6 deletion may represent an under-recognized genomic contributor to idiopathic PG and JM. Prospective studies with tissue-level validation and functional assays are needed to confirm clinical significance and clarify mechanism.