ESPE Abstracts (2022) 95 P2-259

ESPE2022 Poster Category 2 Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology (30 abstracts)

A case of 46, XX female with short stature, primary ovarian insufficiency and kidney dystopia due to two novel mutations in MCM8 gene

Ekaterine Kvaratskhelia 1,2 , Tinatin Tkemaladze 3 , Mariam Chipashvili 4 , Maka Jorbenadze 5 & Guram Chitaia 6

1Department of Endocrinology, Ilia State University, Tbilisi, Georgia; 2Tbilisi State Medical University, Tbilisi, Georgia; 3Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia; 4Department of Pharmacology, Tbilisi State University, Tbilisi, Georgia; 5Department of Public Health, Tbilisi State University, Tbilisi, Georgia; 6Department of Nephrology, Tsitsishvili Pediatric Clinic, Tbilisi, Georgia

Primary ovarian insufficiency (POI) affects about 1% of females under 40 and represents a major cause of female infertility. Approximately one third of POI are of genetic in origin, including FMR1 premutation, Turner syndrome and approximately 60 other genes, involved in development, hormonal signaling, cell division and survival, immunity, and metabolism. MCM8 is a recently discovered gene that plays an important role in homologous recombination and DNA repair and only up to ten mutations have been described in the medical literature so far. Identification of causes of POI is very important for early determination of reproductive prognosis and though for improving reproductive outcomes. We describe a 13-year-old girl, from non-consanguineous family, 1st non-remarkable pregnancy and delivery, born term, 2900 gr and 49 cm. Her linear growth delay was noticed from 8 years and by 11 years it was -2SDs. Body proportions US/LS 0.99. Mild cubitus valgus, hypermobile joints, mild shortening of the 4th metacarpals, hypertrychosis with normal shaped chest and neck were seen phenotypically, intelligence age-appropriate. Bone age was delayed with 3 years. Ultrasound examination revealed rotation of the right kidney and dystopic left kidney, but kidney function remains normal on annual control. Pelvis MRI showed agenesis of ovaries and small hypoechogenic uterus. Thyroid status, serological markers of celiac disease, IGF-1, IGFBP-3 were normal, FSH as well LH were markedly elevated, AMH were extremely low. Cytogenetic analysis confirmed 46,XX karyotype. Whole exome sequencing (WES) was performed, which revealed two novel heterozygous variants in MCM8 gene: c.278_271del, p.(Ile93Argfs*22) and c.703T>C, p.(Cys235Arg). Currently the patient is on transdermal estrogen treatment for 6 months. Her bone age is still delayed with two years, and height velocity remains in prepubertal range, but breast development started and the size of the uterus increased and became more structured. The presented case is noteworthy in several ways. Firstly, it highlights the importance and diagnostic utility of WES in the context of unexplained POI. Secondly, we describe two novel mutations in MCM8 gene, broadening the mutation spectrum of the MCM8-related disorder. Finally, presented case broadens the phenotypic spectrum of this rare disease prompting clinicians to suspect genetic etiology of POI in the context of short stature and kidney malformations.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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