The Experts below are selected from a list of 1740 Experts worldwide ranked by ideXlab platform
Tsutomu Ogata - One of the best experts on this subject based on the ideXlab platform.
-
aromatase excess syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding aromatase results in a rare genetic disorder referred to as aromatase excess syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, Gonadotropin Deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
-
aromatase excess syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding aromatase results in a rare genetic disorder referred to as aromatase excess syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, Gonadotropin Deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
-
de novo frameshift mutation in fibroblast growth factor 8 in a male patient with Gonadotropin Deficiency
2014Co-Authors: Erina Suzuki, Mami Miyado, Shuichi Yatsuga, Maki Igarashi, Kazuhiko Nakabayashi, Keiko Hayashi, Kenichirou Hata, Akihiro Umezawa, Gen Yamada, Tsutomu OgataAbstract:Background/Aims: Missense, nonsense, and splice mutations in the Fibroblast Growth Factor 8 (FGF8) have recently been identified in patients with hypothalamo-pituitary dysfunction and craniofacial anomalies. Here, we report a male patient with a frameshift mutation in FGF8 . Case Report: The patient exhibited micropenis, craniofacial anomalies, and ventricular septal defect at birth. Clinical evaluation at 16 years and 8 months of age revealed delayed puberty, hypos
-
novel mutation of tbx3 in a japanese family with ulnar mammary syndrome implication for impaired sex development
2002Co-Authors: Goro Sasaki, Tsutomu Ogata, Tomohiro Ishii, Tomonobu Hasegawa, Seiji Sato, Nobutake MatsuoAbstract:We report on a Japanese family (two brothers and their mother) with ulnar-mammary syndrome (UMS). Clinical features included hypoplasia or aplasia of upper limbs on the ulnar side in the three affected individuals, micropenis with or without cryptorchidism, and hypoplastic nipples in the brothers; and hypoplastic mammary glands and nipples, poor perspiration, and bicornuate uterus in the mother. Endocrine studies performed for the underdeveloped external genitalia when the brothers were 11 6/12 and 7 2/12 years old, respectively, indicated low to low-normal responses of luteinizing hormone (LH) and follicle stimulating hormone (FSH) to Gonadotropin releasing hormone stimulation tests (elder brother: LH = 2.2 IU/L, FSH = 0.6 --> 2.2 IU/L; younger brother: LH = 3.3 IU/L, FSH = 0.7 --> 4.4 IU/L) and normal testosterone responses to human Gonadotropin stimulation tests (elder brother: 8.8 nmol/L; younger brother: 6.3 nmol/L). Testosterone enanthate therapy (25 mg/dose IM twice) was effective in the brothers, with penile length increase being similar between the brothers (approximately 5 mm/dose) and 23 age-matched boys with idiopathic micropenis (mean 4.4 mm/dose, range 2.5-7.5 mm/dose). Sequence analysis of the TBX3 gene showed a novel heterozygous nonsense mutation (A817T, K273X) in exon 4 of the three patients. The results are consistent with the previous finding that UMS is caused by haploinsufficiency of TBX3, and imply that mild Gonadotropin Deficiency may be the primary cause for underdeveloped external genitalia in males with UMS.
Taneli Raivio - One of the best experts on this subject based on the ideXlab platform.
-
treatment of Gonadotropin Deficiency during the first year of life long term observation and outcome in five boys
2019Co-Authors: Ella Kohva, Johanna Hietamäki, Matti Hero, Päivi J. Miettinen, Taneli Raivio, Hanna HuopioAbstract:Study question What is the peripubertal outcome of recombinant human FSH (r-hFSH) treatment during minipuberty in boys with congenital hypogonadotropic hypogonadism (CHH)? Summary answer Sertoli-cell response to r-hFSH, given during the minipuberty of infancy, appears insufficient to maintain Sertoli cell function throughout childhood, as evaluated by inhibin B measurements. What is known already Severe CHH in boys can be diagnosed during the minipuberty of infancy. Combined Gonadotropin treatment at that age is suggested to improve testicular endocrine function and future fertility, yet long-term evidence is lacking. Study design, size, duration In this retrospective cohort study, we describe five CHH boys treated with r-hFSH in Helsinki University Hospital or Kuopio University Hospital between 2004 and 2018. Immediate follow-up data (0.1-1.4 months after cessation of the Gonadotropin therapy) was available for four boys and long-term observations (at the age of 10.0-12.8 years) was available for three boys. As a retrospective control cohort, we provide inhibin B values of eight untreated CHH boys at the age of 12.7-17.8 years. Participants/materials, setting, methods Four patients had combined pituitary hormone Deficiency, and one had CHARGE syndrome due to a CHD7 mutation. The patients were treated at the age of 0.7-4.2 months with r-hFSH (3.4 IU/kg-7.5 IU/kg per week in 2 or 3 s.c. doses for 3-4.5 months) combined with T (25 mg i.m. monthly for three months for the treatment of micropenis). Inhibin B was chosen as the primary outcome measure. Main results and the role of chance During the r-hFSH + T treatment, inhibin B increased from 76 ± 18 ng/l to 176 ± 80 ng/l (P = 0.04) and penile length increased by 81 ± 50% (P = 0.04). Unexpectedly, two boys with robust inhibin B responses in infancy demonstrated low inhibin B values in peripuberty: declining from 290 ng/l (4 months) to 16 ng/l (12.4 years), and from 207 ng/l (6 months) to 21 ng/l (12.8 years). All boys underwent orchiopexy at 2.0 ± 0.7 years of age. Inhibin B values in long-term follow-up, available for the three boys, did not significantly differ from the untreated CHH controls. Limitations, reasons for caution Limitations of this retrospective study are the small number and heterogeneity of the patients and their treatment schemes. Wider implications of the findings We describe the first long-term follow-up data on CHH boys treated with r-hFSH and T as infants. The results from this small patient series suggest that the effects of infant r-hFSH treatment may be transient, and further longitudinal studies are required to determine the efficacy of this treatment approach to optimise the fertility potential in this patient population. Study funding/competing interest(s) This work was supported by the Finnish foundation for Pediatric Research, the Academy of Finland and the Emil Aaltonen Foundation. The authors have no competing interests. Trial registration number Non-applicable.
-
GnRH receptor gene mutations in adolescents and young adults presenting with signs of partial Gonadotropin Deficiency
2017Co-Authors: Johanna Hietamäki, Matti Hero, Elina Holopainen, Johanna Känsäkoski, Kirsi Vaaralahti, Anna-pauliina Iivonen, Päivi J. Miettinen, Taneli RaivioAbstract:Biallelic, partial loss-of-function mutations in GNRHR cause a wide spectrum of reproductive phenotypes from constitutional delay of growth and puberty to complete congenital hypogonadotropic hypogonadism. We studied the frequency of GNRHR, FGFR1, TAC3, and TACR3 mutations in nine adolescent and young adult females with clinical cues consistent with partial Gonadotropin Deficiency (stalled puberty, unexplained secondary amenorrhea), and describe phenotypic features and molecular genetic findings of monozygotic twin brothers with stalled puberty. Two girls out of nine (22%, 95%CI 6-55%) carried biallelic mutations in GNRHR. The girl with compound heterozygous c.317A>G p.(Gln106Arg) and c.924_926delCTT p.(Phe309del) GNRHR mutations displayed incomplete puberty and clinical signs of hypoestrogenism. The patient carrying a homozygous c.785G>A p.(Arg262Gln) mutation presented with signs of hypoestrogenism and unexplained secondary amenorrhea. None of the patients exhibited mutations in FGFR1, TAC3, or TACR3. The twin brothers, compound heterozygous for GNRHR mutations c.317A>G p.(Gln106Arg) and c.785G>A p.(Arg262Gln), presented with stalled puberty and were discordant for weight, and the heavier of them had lower testosterone levels. These results suggest that genetic testing of the GNRHR gene should be offered to adolescent females with low-normal Gonadotropins and unexplained stalled puberty or menstrual dysfunction. In male patients with partial Gonadotropin Deficiency, excess adipose tissue may suppress hypothalamic-pituitary-gonadal axis.
Jacques Young - One of the best experts on this subject based on the ideXlab platform.
-
sex steroids precursors and metabolite deficiencies in men with isolated hypogonadotropic hypogonadism and panhypopituitarism a gcms based comparative study
2015Co-Authors: Frank Giton, Luigi Maione, Sylvie Braillytabard, Severine Trabado, Julie Sarfati, Yves Le Bouc, Jean Fiet, Jacques YoungAbstract:Context: Both testicular and adrenal steroid secretions are impaired in men with panhypopituitarism (Hypo-Pit), whereas only testicular steroid secretion is impaired in men with isolated Gonadotropin Deficiency (IHH) caused by normosmic congenital hypogonadotropic hypogonadism or Kallmann syndrome. Objective: The objective of the study was to compare the serum levels of sex steroids, precursors, and metabolites between men with complete IHH and those with Hypo-Pit. Patients: We studied 42 healthy men, 16 untreated men with IHH (normosmic congenital hypogonadotropic hypogonadism/Kallmann syndrome) and 23 men with Hypo-Pit (14 with craniopharyngioma, 9 with congenital hypopituitarism) receiving hydrocortisone, thyroxine, and GH replacement therapy but not T. Methods: Gas chromatography/mass spectrometry (GCMS) was used to measure the serum levels of sex steroids [T, dihydrotestosterone (DHT), and estradiol (E2)], their precursors (pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenediol,...
-
two families with normosmic congenital hypogonadotropic hypogonadism and biallelic mutations in kiss1r kiss1 receptor clinical evaluation and molecular characterization of a novel mutation
2013Co-Authors: Frederic Brioude, Sylvie Braillytabard, Jerome Bouligand, Bruno Francou, Jerome Fagart, Ronan Roussel, Say Viengchareun, Laurent Combettes, Marc Lombes, Jacques YoungAbstract:Context KISS1R mutations have been reported in few patients with normosmic congenital hypogonadotropic hypogonadism (nCHH) (OMIM #146110). Objective To describe in detail nCHH patients with biallelic KISS1R mutations belonging to 2 unrelated families, and to functionally characterize a novel KISS1R mutation. Results An original mutant, p.Tyr313His, was found in the homozygous state in 3 affected kindred (2 females and 1 male) from a consanguineous Portuguese family. This mutation, located in the seventh transmembrane domain, affects a highly conserved amino acid, perturbs the conformation of the transmembrane segment, and impairs MAP kinase signaling and intracellular calcium release. In the second family, a French Caucasian male patient with nCHH was found to carry two recurrent mutations in the compound heterozygous state (p.Leu102Pro/Stop399Arg). In this man, pulsatile GnRH (Gonadotropin Releasing Hormone) administration restored pulsatile LH (Luteinizing Hormone) secretion and testicular hormone secretion. Later, long-term combined Gonadotropin therapy induced spermatogenesis, enabling 3 successive pregnancies that resulted in 2 miscarriages and the birth of a healthy boy. Conclusion We show that a novel loss-of-function mutation (p.Tyr313His) in the KISS1R gene can cause familial nCHH, revealing the crucial role of this amino acid in KISS1R function. The observed restoration of Gonadotropin secretion by exogenous GnRH administration further supports, in humans, the hypothalamic origin of the Gonadotropin Deficiency in this genetic form of nCHH.
-
genetics defects in gnrh1 a paradigm of hypothalamic congenital Gonadotropin Deficiency
2010Co-Authors: Jerome Bouligand, Sylvie Braillytabard, Severine Trabado, Cristina Ghervan, Anne Guiochonmantel, Jacques YoungAbstract:Gonadotropin-releasing hormone (GnRH) is a crucial neurohormone regulating puberty and reproduction in non primate mammals, monkeys and humans. This neuropeptide is released in synchronized pulses from the nerve endings of several hundred GnRH neurons into the hypophyseal portal system to stimulate the biosynthesis and secretion of LH and FSH from pituitary gonadotrophs. These two dimeric glycoprotein hormones in turn travel through the circulation to the gonads, stimulating the synthesis and secretion of male and female sex steroid hormones and gametogenesis in both genders. Congenital hypogonadotropic hypogonadism (CHH) is a clinical syndrome that results from a decrease in Gonadotropin secretion and is characterized by a complete or partial lack of pubertal development. CHH is caused mainly by defective GnRH production or release by the hypothalamus or by defective GnRH-receptor function in the pituitary. The syndromes of GnRH Deficiency, either with anosmia or hyposmia, termed Kallmann Syndrome (KS), or with a normal sense of smell, called normosmic non syndromic CHH, (nCHH) are important disease models that have revealed respectively much about the developmental and functional abnormalities that can befall the GnRH neurons. For more than three decades, GNRH1 was an obvious candidate gene for nCHH in human beings. Indeed, in the natural hpg mouse model discovered in 1977, the hypogonadotropic hypogonadal phenotype, secondary to a hypothalamic GnRH Deficiency, was caused by a homozygous deletion within the ortholog Gnrh1 gene. In 2009, homozygous inactivating mutations in the GNRH1 gene causing hypothalamic nCHH patients were at last reported in one female and two young male subjects, validating definitively the pivotal role of GnRH in human pubertal development and reproduction.
Maki Fukami - One of the best experts on this subject based on the ideXlab platform.
-
aromatase excess syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding aromatase results in a rare genetic disorder referred to as aromatase excess syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, Gonadotropin Deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
-
aromatase excess syndrome a rare autosomal dominant disorder leading to pre or peri pubertal onset gynecomastia
2014Co-Authors: Maki Fukami, Makio Shozu, Keisuke Nagasaki, Mami Miyado, Tsutomu OgataAbstract:Abstract Overexpression of CYP19A1 encoding aromatase results in a rare genetic disorder referred to as aromatase excess syndrome (AEXS). Male patients with AEXS manifest pre- or peri-pubertal onset gynecomastia, Gonadotropin Deficiency, and advanced bone age, while female patients are mostly asymptomatic. To date, 30 male patients with molecularly confirmed AEXS have been reported. A total of 12 types of submicroscopic rearrangements, i.e., two simple duplications, four simple deletions, two simple inversions, and four complex rearrangements, have been implicated in AEXS. Clinical severity of AEXS primarily depends on the types of the rearrangements. AEXS appears to account for a small number of cases of pre- or peri-pubertal onset gynecomastia, and should be suspected particularly when gynecomastia is associated with an autosomal dominant inheritance pattern, characteristic hormone abnormalities and/or advanced bone age. Treatment with an aromatase inhibitor appears to benefit patients with AEXS, although long-term safety of this class of drugs remains unknown.
Robert P Kelch - One of the best experts on this subject based on the ideXlab platform.
-
variable x linked recessive hypopituitarism with evidence of Gonadotropin Deficiency in two pre pubertal males
2008Co-Authors: William B Zipf, Robert P Kelch, George E BaconAbstract:Two half-brothers with short stature secondary to growth hormone Deficiency and a family history implicating X-linked transmission were studied extensively for other endocrine abnormalities. The proband had a normal physical examination, except for small stature and small external genitalia. ACTH and TSH release were normal. LH and FSH responses during an i.v. GnRH test were severely blunted. His half-brother also had a normal physical examination, except for severe short stature and very small external genitalia. Deficiencies of ACTH, and TSH as well as GH were documented. An i.v. GnRH test showed no LH or FSH response. These studies support the existence of an X-linked recessive form of hypopituitarism and portend the clinical usefulness of the i.v. GnRH test in evaluating Gonadotropin reserve.
-
congenital adrenal hypoplasia and isolated Gonadotropin Deficiency
1991Co-Authors: Gad B Kletter, Jerome L Gorski, Robert P KelchAbstract:Abstract Congenital adrenal hypoplasia with Gonadotropin Deficiency is a rare X-linked recessive disorder that usually manifests with symptoms of adrenal insufficiency early in infancy. Adequate replacement therapy with glucocorticoids, mineralocorticoids, and salt has resulted in an increased survival. Slow growth and failure to undergo sexual maturation during the adolescent years usually ensues, secondary to hypogonadotropic hypogonadism. The X-linked congenital adrenal hypoplasia locus has been mapped to region Xp21.3-p21.2. Interstitial deletions of the X chromosome overlapping this region have been observed to cause complex clinical problems, with adrenal hypoplasia as a prominent component. Within a family segregating the disease, there is a 50% risk of having an affected male and a 50% risk of having a carrier female; considerations of genetic heterogeneity, possible chromosomal abnormalities, and prenatal diagnostic studies warrant medical genetic evaluations. The following case presentations illustrate the clinical spectrum of this condition.