Genetic sequencing of a patient with Kallmann syndrome plus 5α-reductase type 2 deficiency

Ji, Wen T.; Zhang, Luyao; Li, Fucheng; Wang, Yu; He, Wei; Yin, Qi-Qi; Liao, Zhi-Hong

doi:10.4103/1008-682x.170865

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…In 2017, Ji et al reported that a 28-year-old KS patient presented with no signs of puberty, bilateral cryptorchidism, olfactory loss, and right deafness. Genetic tests found that in addition to nonpathogenic variants (rs808119, rs6185) of ANOS1 and GNRH1, SRD5A2 gene heterozygous variation (c.680G > A) was also present, and T/DHT was 26.40, after the hCG test; thus, it was considered that the patient had KS and 5 α-RD [40]. In Indonesia, 11 patients with 46, XY DSDs were reported to carry pathogenic mutations, including PROKR2, PROK2, WDR11, FGFR1, and CHD7 mutations, and these patients had different degrees of hypospadias [41].…”

Section: Discussionmentioning

confidence: 99%

The Clinical and Genetic Characteristics of Chinese Male Pediatric Patients with Congenital Hypogonadotropic Hypogonadism

Wang

Qin

Fan

et al. 2021

Preprint

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Purpose：Congenital hypogonadotropic hypogonadism (CHH) are invided into Kallmann Syndrome (KS) and normosmic HH(nHH). The clinical and genetic characteristics of CHH are more studied in adults, but less in pre-adults. Methods: Medical records of 126 patients with CHH at our hospital during 2008−2020 were evaluated. Results: Totally, seven patients (5.6%) had hypospadias. Among 49 patients with positive family history, delayed puberty, KS/nHH and olfactory abnormalities accounted for 44.9%, 16.3%, and 12.2%, respectively. Sixty-five patients completed the hCG prolongation test, and T levels of 24 patients were lower than 100 ng/dl. 25 CHH-related genes were found in 78 patients, digenic mutations in 23 patients, and trigenic mutations in 3 patients. The most common pathogenic genes were FGFR1 (21.1%), PROKR2 (17.9%), ANOS1 (12.6%) and CHD7 (12.6%). The oligogenicity rate of common autosomal dominant heredity genes accounted for 50.0% (FGFR1, 10/20) and 33.3% (CHD7, 4/12), of autosomal recessive heredity gene PROKR2 accounted for 47.1% (8/17). And W178S accounted for 58.8% of all mutations in PROKRR2.Conclusion: Micropenis and cryptorchidism are important cues for CHH in pre-adulthood; hypospadias is a rare phenotype of CHH. At least 22.9% of patients tested had testicular Leydig cell dysfunction (dual CHH). Oligogenic mutations were found in 27.4% of all patients with CHH. W178S in PROKRR2 maybe a founder mutation in Chinese CHH crowds.

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Section: Discussionmentioning

confidence: 99%

The Clinical and Genetic Characteristics of Chinese Male Pediatric Patients with Congenital Hypogonadotropic Hypogonadism

Wang

Qin

Fan

et al. 2021

Preprint

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Correlation Analysis of Genotypes and Phenotypes in Chinese Male Pediatric Patients With Congenital Hypogonadotropic Hypogonadism

et al. 2022

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Congenital hypogonadotropic hypogonadism (CHH) can be divided into Kallmann syndrome (KS) and normosmic HH (nHH). The clinical and genetic characteristics of CHH have been studied in adults, but less in pre-adults. The medical records of patients with CHH in our gonad disease database from 2008 to 2020 were evaluated. In total, 125 patients aged 0 to 18 years were enrolled in our study. KS patients had a higher incidence of micropenis compared with nHH (86.2% vs. 65.8%, p=0.009), and 7 patients (5.6%) had hypospadias. Among the 39 patients with traceable family history, delayed puberty, KS/nHH, and olfactory abnormalities accounted for 56.4%, 17.9%, and 15.4%, respectively. In total, 65 patients completed the hCG prolongation test after undergoing the standard hCG test, and the testosterone levels of 24 patients (22.9%) were still lower than 100 ng/dL. In 77 patients, 25 CHH-related genes were identified, including digenic and trigenic mutations in 23 and 3 patients, respectively. The proportion of oligogenic mutations was significantly higher than that in our previous study (27.7% vs. 9.8%). The most common pathogenic genes were FGFR1, PROKR2, CHD7 and ANOS1. The incidence rate of the genes named above was 21.3%, 18.1%, 12.8% and 11.7%, respectively; all were higher than those in adults (<10%). Most mutations in CHH probands were private, except for W178S in PROKR2, V560I in ANOS1, H63D in HS6ST1, and P191L and S671L in IL17RD. By analyzing family history and genes, we found that both PROKR2 and KISS1R may also be shared between constitutional delay of growth and puberty (CDGP) and CHH. L173R of PROKR2 accounts for 40% of the CHH population in Europe and the United States; W178S of PROKR2 accounts for 58.8% of Chinese CHH patients. Micropenis and cryptorchidism are important cues for CHH in children. They are more common in pediatric patients than in adult patients. It is not rare of Leydig cell dysfunction (dual CHH), neither of oligogenic mutations diagnosed CHH in children. Both PROKR2 and KISS1R maybe the potential shared pathogenic genes of CDGP and CHH, and W178S in PROKR2 may be a founder mutation in Chinese CHH patients.

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Genetic sequencing of a patient with Kallmann syndrome plus 5α-reductase type 2 deficiency

Cited by 2 publications

References 10 publications

The Clinical and Genetic Characteristics of Chinese Male Pediatric Patients with Congenital Hypogonadotropic Hypogonadism

The Clinical and Genetic Characteristics of Chinese Male Pediatric Patients with Congenital Hypogonadotropic Hypogonadism

Correlation Analysis of Genotypes and Phenotypes in Chinese Male Pediatric Patients With Congenital Hypogonadotropic Hypogonadism

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