Objective: To compare the efficiency of the target gene panel method and whole-exome sequencing (WES) in detecting idiopathic hypogonadotropic hypogonadism (IHH), and select a more suitable gene detection method. METHODS: We selected 24 genes closely related to the molecular pathogenesis of IHH to make up the gene panel, detected the mutation sites in 73 patients with IHH using the panel method, and verified the results of sequencing with the Sanger method. Using the key words "idiopathic hypogonadotropic hypogonadism", we searched databases for relevant literature, calculated the positive rate of IHH detected by WES and compared it with that detected with the panel method. RESULTS: Of the 73 cases of IHH detected with the panel method, 7 were found with pathogenic mutations, including 2 cases of FGFR1, 2 cases of CHD7, 2 cases of KISS1R, and 1 case of NR5A1 mutation. Sanger sequencing showed that the positive rate of the panel method was 9.7%. Of the 1 336 articles retrieved, 5 met the inclusion criteria and were included, in which WES revealed a positive rate of about 30%. CONCLUSIONS For detection of the diseases with clear mutated genes, the panel method is relatively inexpensive and has a high sequencing depth, while for detection of the diseases with complicated genetic patterns and unclear mutated genes, WES is more efficient. Further studies are needed for choice of the two methods for different purpose of detection./.
Humans ; Hypogonadism/genetics* ; Male ; Whole Exome Sequencing

Humans ; Genetic Counseling ; Consensus ; Hypogonadism/genetics*

Child ; Humans ; Genetic Counseling ; Hypogonadism/genetics*

Adult ; Epilepsy ; genetics ; Humans ; Hyperhomocysteinemia ; genetics ; Hypogonadism ; genetics ; Intellectual Disability ; genetics ; Male ; White Matter ; pathology

Adult ; Azoospermia ; genetics ; Chromosomes, Human, Pair 13 ; genetics ; Chromosomes, Human, Pair 14 ; genetics ; Humans ; Hypogonadism ; genetics ; Male ; Translocation, Genetic

The transcription factor SOX10, as a major actor in the development of the neural crest, plays a key role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation. Abnormalities of neural crest development in humans lead to a number of genetic diseases known as neurocristopathies or neural crest disorders. The mutation of SOX10 can cause Kallmann syndrome (KS), which is a clinically and genetically heterogeneous condition and defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Since then, there have been a number of related reports that mutation of SOX10 will lead to KS with deafness. This review focuses on the SOX10 gene and the advances in the diagnosis and genetic studies of KS with deafness caused by the mutatuin of SOX10.
Cell Differentiation ; Deafness ; genetics ; Gonadotropin-Releasing Hormone ; Humans ; Hypogonadism ; Kallmann Syndrome ; genetics ; Mutation ; genetics ; SOXE Transcription Factors ; genetics

OBJECTIVE: To explore the etiology of a patient with Kallmann syndrome (congenital hypogonadism and anosmia) and a 45,X/46,XY karyotype. METHODS: Peripheral venous blood samples were collected from the proband and his parents and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The proband was found to harbor compound heterozygous variants of the PROKR2 gene, namely c.533G>C (p.W178S) and c.308C>T (p.A103V), which were inherited from his father and mother, respectively. The two variants were respectively predicted to be likely pathogenic and variant of unknown significance, respectively. CONCLUSION The reduced chromosomal mosaicism might have caused no particular clinical manifestations in this patient. For patients with features of Kallmann syndrome, genetic testing is conducive to early diagnosis and can provide a basis for genetic counseling and clinical treatment.
Humans ; Genetic Testing ; Hypogonadism/genetics* ; Kallmann Syndrome/genetics* ; Karyotype ; Mutation ; Exome Sequencing ; Chromosomes, Human, X/genetics* ; Chromosomes, Human, Y/genetics*

Klinefelter's syndrome is one of the most common forms of primary hypogonadism and infertility in males. It is characterized by small and firm testes, gynecomastia, azoospermia, and an elevated gonadotropin level. The frequencies of diabetes mellitus, breast cancer, and germ cell neoplasia increases in Klinefelter's syndrome. We report upon a 35 year-old male patient with Graves' disease in association with Klinefelter's syndrome; as confirmed by chromosome analysis. The patient is being treated with antithyroid medication for Graves' disease and by testosterone replacement for Klinefelter's syndrome.
Adult ; Graves' Disease/*etiology/radionuclide imaging ; Human ; Hypogonadism/*etiology/genetics/pathology ; Klinefelter Syndrome/*complications/genetics/pathology ; Male

OBJECTIVETo analyze the association of the androgen receptor (AR) gene CAG-STR with late-onset hypogonadism (LOH), and explore the pathogenesis of LOH.

METHODSOur investigation involved 1 000 men aged 40-70 years. We randomly selected 127 normal old and middle-aged males and 19 cases of LOH. We detected their levels of Triglyceride (TG), fasting blood glucose (FBG), serum total testosterone (tT) and free testosterone (fT), measured their body mass index (BMI), height, waist circumference (WC) and blood pressure, and examined the length of CAG repeats of the AR gene in the peripheral blood by PCR.

RESULTSThe numbers of CAG repeats ranged from 15 to 32, with a mean value 23.05 +/- 2.95. The mean BMI and FBG were significantly lower (P < 0.01), but TG, tT and fT remarkably higher in the normal than in the LOH men (P < 0.01), while the mean length of (CAG) n repeat polymorphism showed no statistically significant difference between the two groups (22.54 +/- 3.06 vs 23.23 +/- 2.24, P = 0.946). The frequencies of long alleles (n > or = 22) were significantly higher in the LOH than in the normal men (73.68% vs 48.82%, P < 0.05). The numbers of CAG repeats had no significant correlation with tT (r = 0.04, P > 0.05) and fT (r = 0.025, P > 0.05).

CONCLUSIONThe AR gene CAG length showed polymorphism in LOH men. The long alleles (CAG)n (n > or = 22) repeat polymorphism in the AR gene may be a genetic factor for LOH, but it has to be confirmed by further investigation.

Adult ; Aged ; Alleles ; Gene Dosage ; Humans ; Hypogonadism ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Androgen ; genetics ; Trinucleotide Repeats

Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of PHF6 gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the PHF6 (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.
Humans ; Male ; Female ; Child ; Infant ; Intellectual Disability/genetics* ; Mental Retardation, X-Linked/pathology* ; Obesity/complications* ; Hypogonadism/pathology*