Homozygosity for a novel INHA mutation in two male siblings with hypospadias, primary hypogonadism, and high-normal testicular volume
| Autor: | Esra Arslan Ates, Mehmet Eltan, Bahadir Sahin, Busra Gurpinar Tosun, Tuba Seven Menevse, Bilgen Bilge Geckinli, Andy Greenfield, Serap Turan, Abdullah Bereket, Tulay Guran |
|---|---|
| Přispěvatelé: | Arslan Ateş E., Eltan M., Sahin B., Gurpinar Tosun B., Seven Menevse T., Geckinli B. B., Greenfield A., Turan S., Bereket A., Güran T. |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
Endocrinology Diabetes and Metabolism Medicine (miscellaneous) Assessment and Diagnosis Sağlık Bilimleri Temel Bilgi ve Beceriler Genel Tıp Pediatrics Pathophysiology Clinical Medicine (MED) Çocuk Sağlığı ve Hastalıkları Child Health and Diseases Endocrinology TIP GENEL & DAHİLİ Testis Health Sciences Internal Medicine Humans Inhibins Klinik Tıp (MED) Pediatri Perinatoloji ve Çocuk Sağlığı Aile Sağlığı MEDICINE GENERAL & INTERNAL Pediatric Endocrinology and Metabolism Dahiliye Patofizyoloji Hypospadias Internal Medicine Sciences Klinik Tıp Hypogonadism Siblings Fundamentals and Skills Dahili Tıp Bilimleri General Medicine CLINICAL MEDICINE Değerlendirme ve Teşhis Tıp Pediatri Mutation General Health Professions Pediatrics Perinatology and Child Health Medicine Female PEDİATRİ Tıp (çeşitli) Family Practice Pediatrik Endokrinoloji ve Metabolizma Genel Sağlık Meslekleri |
| Popis: | 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 INHAmutations. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|