ESPE Abstracts (2023) 97 P2-316

FSBEI FPE RMACPE MOH, Moscow, Russian Federation

Introduction: One of the strategies of searching the genetic causes of CDGP is analysing the genes responsible for hypogonadotropic hypogonadism (HH).

Objective: To investigate the role of the HS6ST1 gene in development CDGP.

Materials and Methods: Two patients - height and BMI SDS, bone age, genitometric parameters, basal hormones, GnRH analogue test, hCG test, olfactometry, brain-MRI. Four patients (two sisters, brother, mother) - molecular genetic study, parallel sequencing (IonTorent platform), custom Ampliseq_HH panel: FGF8, NELF, SEMA3A, KISS1, KAl2, KAL1, TACR3, WDR11, GREAT, GNRH1, TAC3, KAL4, NR0B1, LHB, PROKR2, GNRHR, KISS1R, CHD7, HS6ST1, INSL3, IL17RD, SPRY4, FGF17, DUSP6, FLRT3, DNMT3L, POLR3A, POLR3B, RBM28, MKRN3.


Patient 1: male, 13.9 years (proband), Tanner P1G1, height -1.86sd, BMI -2.1sd, bone age 12.5 years, LH 0.1 mIU/ml, FSH 1.22 mIU/ml, total testosterone < 0.1 ng/ml, inhibin B 56.6 pg/ml, AMH 119.5 ng/ml, prolactin 3.93 ng/ml, TSH 1.81 mIU/ml, T4 15.27 pmol/l, IGF1 195.4 ng/ml, GnRH analogue test - LH 10.59 mIU/ml; hCG test testosterone 6.5 nmol/l. Olfactometry - mixed hyposmia. Brain-MRI - pituitary hypoplasia. Age 16.3 years, Tanner P2G2, height -2.4sd, cycle of testosterone esters 100 mg/month for 3 months. Age 20.1 years, height 174 cm, Tanner P5G5, testosterone 17.68 nmol/l, inhibin B 274.3 pg/ml.

Patient 2: female, 13.3 years (sister of the proband), Tanner P1B2, height -1.97sd, BMI -1.72sd, bone age 11 years, LH 4.34 mIU/ml, FSH 4.28 mIU/ml, estradiol 11.2 pg/ml, TSH 2.39 μIU/ml, T4 1.31 ng/dl, IGF-1 188.2 ng/ml, AMH 5.49 ng/ml, the volume of the uterus 1.0 ml, ovary - 3.8 ml/2.2 ml, GnRH analogue test LH/FSH max. 7.72/13.16 mIU/ml. Age at menarche 15.5 once, then wasn't any menstruations during 6 months.

Patient 3: female (sister of the proband): menarche from 15.5 years, regular. Father and mother have under timely sexual development. The heterozygous substitution c.652C>T:p.P218S with unknown pathogenicity in the HS6ST1 gene (MIM♯:604846, reference sequence (NM_004807) was found in a brother and two sisters and was not in the mother.

Conclusions: Three members of the family showed CDGP of varying severity and the same heterozygous substitution in the HS6ST1 gene with unknown pathogenicity. Clarification of the genetic causes of HH and CDGP will improve the diagnosis of the causes of delayed sexual development. The study of genes associated with HH is one of the strategies for determining the genetic causes of CDGP.

Volume 97

61st Annual ESPE (ESPE 2023)

The Hague, Netherlands
21 Sep 2023 - 23 Sep 2023

European Society for Paediatric Endocrinology 

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