scholarly journals Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann syndrome

2016 ◽  
Vol 437 ◽  
pp. 86-96 ◽  
Author(s):  
Samuel D. Quaynor ◽  
Maggie E. Bosley ◽  
Christina G. Duckworth ◽  
Kelsey R. Porter ◽  
Soo-Hyun Kim ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Candidate Genes ◽  
Hypogonadotropic Hypogonadism ◽  
Kallmann Syndrome ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Generation Sequencing

Targeted next-generation sequencing (NGS) of nine candidate genes with custom AmpliSeq in patients and a cardiomyopathy risk group

2015 ◽  
Vol 446 ◽  
pp. 132-140 ◽  
Author(s):  
Andrey S. Glotov ◽  
Sergey V. Kazakov ◽  
Elena A. Zhukova ◽  
Anton V. Alexandrov ◽  
Oleg S. Glotov ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Candidate Genes ◽  
Risk Group ◽  
Next Generation ◽  
Targeted Next Generation Sequencing ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

scholarly journals GENETICS IN ENDOCRINOLOGY: Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing

2018 ◽  
Vol 178 (3) ◽  
pp. R55-R80 ◽  
Author(s):  
Luigi Maione ◽  
Andrew A Dwyer ◽  
Bruno Francou ◽  
Anne Guiochon-Mantel ◽  
Nadine Binart ◽  
...  
Keyword(s):  
Genetic Counseling ◽  
Next Generation Sequencing ◽  
Pubertal Development ◽  
Hypogonadotropic Hypogonadism ◽  
Kallmann Syndrome ◽  
Incomplete Penetrance ◽  
Next Generation ◽  
Congenital Hypogonadotropic Hypogonadism ◽  
Main Challenge ◽  
Generation Sequencing

Congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS) are rare, related diseases that prevent normal pubertal development and cause infertility in affected men and women. However, the infertility carries a good prognosis as increasing numbers of patients with CHH/KS are now able to have children through medically assisted procreation. These are genetic diseases that can be transmitted to patients’ offspring. Importantly, patients and their families should be informed of this risk and given genetic counseling. CHH and KS are phenotypically and genetically heterogeneous diseases in which the risk of transmission largely depends on the gene(s) responsible(s). Inheritance may be classically Mendelian yet more complex; oligogenic modes of transmission have also been described. The prevalence of oligogenicity has risen dramatically since the advent of massively parallel next-generation sequencing (NGS) in which tens, hundreds or thousands of genes are sequenced at the same time. NGS is medically and economically more efficient and more rapid than traditional Sanger sequencing and is increasingly being used in medical practice. Thus, it seems plausible that oligogenic forms of CHH/KS will be increasingly identified making genetic counseling even more complex. In this context, the main challenge will be to differentiate true oligogenism from situations when several rare variants that do not have a clear phenotypic effect are identified by chance. This review aims to summarize the genetics of CHH/KS and to discuss the challenges of oligogenic transmission and also its role in incomplete penetrance and variable expressivity in a perspective of genetic counseling.

scholarly journals Targeted Next-Generation Sequencing Identifies Separate Causes of Hearing Loss in One Deaf Family and Variable Clinical Manifestations for the p.R161C Mutation in SOX10

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Xiaoyu Yu ◽  
Yun Lin ◽  
Hao Wu
Keyword(s):  
Hearing Loss ◽  
Next Generation Sequencing ◽  
Hypogonadotropic Hypogonadism ◽  
Family Members ◽  
Clinical Manifestations ◽  
Next Generation ◽  
Chinese Han ◽  
Targeted Next Generation Sequencing ◽  
Wide Range ◽  
Generation Sequencing

Hearing loss is the most common sensory deficit in humans. Identifying the genetic cause and genotype-phenotype correlation of hearing loss is sometimes challenging due to extensive clinical and genetic heterogeneity. In this study, we applied targeted next-generation sequencing (NGS) to resolve the genetic etiology of hearing loss in a Chinese Han family with multiple affected family members. Targeted sequencing of 415 deafness-related genes identified the heterozygous c.481C>T (p.R161C) mutation in SOX10 and the homozygous c.235delC (p.L79Cfs∗3) mutation in GJB2 as separate pathogenic mutations in distinct affected family members. The SOX10 c.481C>T (p.R161C) mutation has been previously reported in a Caucasian patient with Kallmann syndrome that features congenital hypogonadotropic hypogonadism with anosmia. In contrast, family members carrying the same p.R161C mutation in this study had variable Waardenburg syndrome-associated phenotypes (hearing loss and/or hair hypopigmentation) without olfactory or reproductive anomalies. Our results highlight the importance of applying comprehensive diagnostic approaches such as NGS in molecular diagnosis of hearing loss and show that the p.R161C mutation in SOX10 may be associated with a wide range of variable clinical manifestations.

Sign in / Sign up

Export Citation Format

Share Document