Hypogonadotropic hypogonadism in a female patient previously diagnosed as having waardenburg syndrome due to a sox10 mutation

Endocrine ◽  
2014 ◽  
Vol 49 (2) ◽  
pp. 553-556 ◽  
Author(s):  
Yoko Izumi ◽  
Ikuma Musha ◽  
Erina Suzuki ◽  
Manami Iso ◽  
Tomoko Jinno ◽  
...  
Keyword(s):  
Female Patient ◽  
Hypogonadotropic Hypogonadism ◽  
Waardenburg Syndrome

scholarly journals A novel SOX10 variant in a Japanese girl with Waardenburg syndrome type 4C and Kallmann syndrome

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Junpei Hamada ◽  
Fumihiro Ochi ◽  
Yuka Sei ◽  
Koji Takemoto ◽  
Hiroki Hirai ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Hypogonadotropic Hypogonadism ◽  
Hirschsprung Disease ◽  
Kallmann Syndrome ◽  
Syndrome Type ◽  
Waardenburg Syndrome ◽  
First Case ◽  
Iris Depigmentation ◽  
Bilateral Sensorineural Hearing Loss

AbstractWe report the first case of Waardenburg syndrome type 4C and Kallmann syndrome in the same person. The patient, a Japanese girl, presented with bilateral iris depigmentation, bilateral sensorineural hearing loss, Hirschsprung disease, hypogonadotropic hypogonadism, and anosmia. We identified a novel SOX10 variant, c.124delC, p.Leu42Cysfs*67.

scholarly journals Kallmann Syndrome Due to Heterozygous Mutation in SOX10 Coexisting With Waardenburg Syndrome Type II: Case Report and Review of Literature

2021 ◽  
Vol 11 ◽  
Author(s):  
Kan Chen ◽  
Haoyu Wang ◽  
Yaxin Lai
Keyword(s):  
Amino Acid ◽  
Pituitary Gland ◽  
Sequence Data ◽  
Hypogonadotropic Hypogonadism ◽  
Clinical Manifestations ◽  
Kallmann Syndrome ◽  
Syndrome Type ◽  
Type Ii ◽  
Waardenburg Syndrome ◽  
Pathogenic Gene

IntroductionKallmann syndrome (KS) is idiopathic hypogonadotropic hypogonadism with olfactory loss or decline. Waardenburg syndrome type II (WS2) is a clinically and genetically heterogeneous disease, characterized by congenital sensorineural deafness and abnormal pigmentation of the iris, hair, and skin. Recently, mutations in the well-known WS pathogenic gene SOX10 have been found in some KS patients with deafness, but whether SOX10 is a co-pathogenic gene of KS and WS remains uncertain. Here, we report a rare case of KS and WS2 co-occurrence due to SOX10 mutations.MethodsDetailed histories were collected through questionnaires and physical examination. Blood samples of the patient and his family members were collected after obtaining informed consents. Suspected mutations were amplified and verified by Sanger sequencing after the next generation sequencing of related genes. The raw sequence data were compared to the known gene sequence data in publicly available sequence data bases using Burrows-Wheeler Aligner software (BWA, 0.7.12-r1039).ResultsA 28-year-old male patient sought treatment for hypogonadism and the absence of secondary sexual characteristics. In addition, he showed signs of obesity, hyposmia, sensorineural hearing loss, and blue iris. Magnetic resonance imaging (MRI) of the olfactory bulb showed small bilateral olfactory bulbs and tracts and diaphragma cerebri. MRI of the pituitary gland revealed a flat pituitary gland in the sella. Laboratory examination demonstrated hypogonadotropic hypogonadism, pituitary hypothyroidism, subclinical hypothyroidism, and the presence of insulin resistance with normal blood glucose levels. Sequencing of the SOX10 gene showed a 20 bp insertion in between coding bases 1,179 and 1,180 (c.1179_1180insACTATGGCTCAGCCTTCCCC). This results in a frame-shifting mutation of the 394th amino acid serine in exon4 with the resulting the amino acid sequence of the protein predicted to be TMAQPSP PSPAPSLTTL TISPQDPIMA TRARPLASTR PSPIWGPRSG PSTRPSLTPA PQGPSPTAPH TGSSQYIRHC PGPKGGPVAT TPRPAPAPSL CALFLAHLRP GGGSGGG*.ConclusionSOX10 plays an important role in some critical stages of neural crest cell development and SOX10 mutation may be a common pathogenic factor for both KS and WS. Therefore, SOX10 mutation analysis should be considered for KS patients with combined WS clinical manifestations, especially deafness.

scholarly journals A novel SOX10 nonsense mutation in a patient with Kallmann syndrome and Waardenburg syndrome

2021 ◽  
Vol 2021 ◽  
Author(s):  
Tetsuji Wakabayashi ◽  
Akihito Takei ◽  
Nobukazu Okada ◽  
Miki Shinohara ◽  
Manabu Takahashi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Neural Crest ◽  
Nonsense Mutation ◽  
Hypogonadotropic Hypogonadism ◽  
Neural Crest Cells ◽  
Kallmann Syndrome ◽  
List Type ◽  
Waardenburg Syndrome ◽  
Common Pathway ◽  
Causative Gene

Summary The underlying genetic drivers of Kallmann syndrome, a rare genetic disorder characterized by anosmia and hypogonadotropic hypogonadism due to impairment in the development of olfactory axons and in the migration of gonadotropin-releasing hormone (GNRH)-producing neurons during embryonic development, remain largely unknown. SOX10, a key transcription factor involved in the development of neural crest cells and established as one of the causative genes of Waardenburg syndrome, has been shown to be a causative gene of Kallmann syndrome. A 17-year-old male patient, who was diagnosed with Waardenburg syndrome on the basis of a hearing impairment and hypopigmented iris at childhood, was referred to our department because of anosmia and delayed puberty. As clinical examination revealed an aplastic olfactory bulb and hypogonadotropic hypogonadism, we diagnosed him as having Kallmann syndrome. Incidentally, we elucidated that he also presented with subclinical hypothyroidism without evidence of autoimmune thyroiditis. Direct sequence analysis detected a nonsense SOX10 mutation (c.373C>T, p.Glu125X) in this patient. Since this nonsense mutation has never been published as a germline variant, the SOX10 substitution is a novel mutation that results in Kallmann syndrome and Waardenburg syndrome. This case substantiates the significance of SOX10 as a genetic cause of Kallmann syndrome and Waardenburg syndrome, which possibly share a common pathway in the development of neural crest cells. Learning points Kallmann syndrome and Waardenburg syndrome possibly share a common pathway during neural crest cell development. SOX10, a key transcription factor involved in the development of neural crest cells, is a common causative gene of Kallmann syndrome and Waardenburg syndrome. Careful evaluation about various phenotypic features may reveal the unknown genetic drivers of Kallmann syndrome.

Hypogonadotropic hypogonadism in a female patient with congenital arhinia

2017 ◽  
Vol 30 (1) ◽  
Author(s):  
Janel Darcy Hunter ◽  
Melissa Ann Davis ◽  
Jennifer Rachel Law
Keyword(s):  
Female Patient ◽  
Hypogonadotropic Hypogonadism ◽  
Brain Magnetic Resonance Imaging ◽  
Abdominal Ultrasound ◽  
Sex Steroid ◽  
Laboratory Evaluation ◽  
Delayed Puberty ◽  
Timely Initiation ◽  
Normal Pituitary Gland ◽  
First Case

AbstractThe association of anosmia and congenital hypogonadotropic hypogonadism (CHH) is well described; however, congenital arhinia is a malformation associated with CHH that occurs much more rarely. There have been three reports of male patients with hypogonadism and congenital arhinia in the literature to date. We present the first case of arhinia associated with CHH in a female patient. A 14 years and 8 months female with congenital arhinia presented with delayed puberty. Physical examination and laboratory evaluation were consistent with hypogonadotropic hypogonadism. She had no other hormone deficiencies and brain magnetic resonance imaging demonstrated a normal pituitary gland. Abdominal ultrasound showed a prepubertal uterus and ovaries. She was subsequently started on sex steroid treatment to induce secondary sexual characteristics. This case demonstrates that abnormalities of nasal development may provide an early diagnostic clue to hypogonadotropic hypogonadism, particularly in female patients who would not manifest classic signs of CHH in infancy (micropenis and cryptorchidism). Early diagnosis of CHH and timely initiation of sex steroid therapy is important to prevent comorbidities related to pubertal delay.

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