Publication: Homozygosity for a novel INHA mutation in two male siblings with hypospadias, primary hypogonadism, and high-normal testicular volume
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Date
2022-03-23
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Abstract
Background: The human INHA gene encodes the inhibin subunit alpha protein, which is common to both inhibin A
and B. The functional importance of inhibins in male sex development, sexual function, and reproduction remain
largely unknown.
Objective: We report for the first time two male siblings with homozygous INHA mutations.
Methods: The medical files were examined for clinical, biochemical, and imaging data. Genetic analysis was performed
using next-generation and Sanger sequencing methods.
Results: Two brothers complained of gynecomastia, testicular pain, and had a history of hypospadias. Biochemistry
revealed low serum testosterone, high gonadotropin and anti-Mullerian hormone, and very low/undetectable
inhibin concentrations, where available. Both patients had azoospermia in the spermiogram. We have identified
a homozygous 2 bp deletion (c.208_209delAG, R70Gfs*3) variant, which leads to a truncated INHA protein in both
patients, and confirmed heterozygosity in the parents. The external genital development, pubertal onset and
progression, reproductive functions, serum gonadotropins, and sex hormones of mother and father, who were
heterozygous carriers of the identified mutation, were normal.
Conclusion: Homozygosity for INHA mutations causes decreased prenatal and postnatal testosterone production and
infertility in males, while the heterozygous female and male carriers of INHA mutations do not have any abnormality in
sex development and reproduction.
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Tıp, Dahili Tıp Bilimleri, Çocuk Sağlığı ve Hastalıkları, Pediatrik Endokrinoloji ve Metabolizma, Sağlık Bilimleri, Medicine, Internal Medicine Sciences, Child Health and Diseases, Pediatric Endocrinology and Metabolism, Health Sciences, Klinik Tıp (MED), Klinik Tıp, PEDİATRİ, TIP, GENEL & DAHİLİ, Clinical Medicine (MED), CLINICAL MEDICINE, PEDIATRICS, MEDICINE, GENERAL & INTERNAL, Genel Sağlık Meslekleri, Pediatri, Patofizyoloji, Temel Bilgi ve Beceriler, Değerlendirme ve Teşhis, Pediatri, Perinatoloji ve Çocuk Sağlığı, Dahiliye, Aile Sağlığı, Tıp (çeşitli), Genel Tıp, General Health Professions, Pediatrics, Pathophysiology, Fundamentals and Skills, Assessment and Diagnosis, Pediatrics, Perinatology and Child Health, Internal Medicine, Family Practice, Medicine (miscellaneous), General Medicine
Citation
Arslan Ateş E., Eltan M., Sahin B., Gurpinar Tosun B., Seven Menevse T., Geckinli B. B., Greenfield A., Turan S., Bereket A., Güran T., "Homozygosity for a novel INHA mutation in two male siblings with hypospadias, primary hypogonadism, and high-normal testicular volume.", European journal of endocrinology, cilt.186, sa.5, 2022