Identification of ROBO1/2 and SCEL as candidate genes in Kallmann syndrome with emerging bioinformatic analysis

Zhu, Zuobin; Han, Xing; Han, Conghui; Deng, Mengqiong; Zhang, Yuhao; Shen, Qing; Cao, Yijuan; Li, Zhenbei; Wang, Xitao; Gu, Juan; Liu, Xiaoyan; Yang, Yaru; Zhang, Qiang; Hu, Fangfang

doi:10.1007/s12020-019-02010-y

Cited by 9 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, a chromosomal translocation t(3;13)(p13;q32) was reported to disrupt ROBO1 (Roundabout Guidance Receptor 1), ROBO2 and SCEL genes in a single patient with KS [236]. However, murine studies in compound Robo1/Robo2 mutant mice did not reveal gross defects in the establishment of the GnRH neuronal system [237].…”

Section: Additional Genesmentioning

confidence: 99%

The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency

Oleari

Massa

Cariboni

et al. 2021

IJMS

View full text Add to dashboard Cite

Gonadotropin releasing hormone (GnRH) neurons are hypothalamic neuroendocrine cells that control sexual reproduction. During embryonic development, GnRH neurons migrate from the nose to the hypothalamus, where they receive inputs from several afferent neurons, following the axonal scaffold patterned by nasal nerves. Each step of GnRH neuron development depends on the orchestrated action of several molecules exerting specific biological functions. Mutations in genes encoding for these essential molecules may cause Congenital Hypogonadotropic Hypogonadism (CHH), a rare disorder characterized by GnRH deficiency, delayed puberty and infertility. Depending on their action in the GnRH neuronal system, CHH causative genes can be divided into neurodevelopmental and neuroendocrine genes. The CHH genetic complexity, combined with multiple inheritance patterns, results in an extreme phenotypic variability of CHH patients. In this review, we aim at providing a comprehensive and updated description of the genes thus far associated with CHH, by dissecting their biological relevance in the GnRH system and their functional relevance underlying CHH pathogenesis.

show abstract

Section: Additional Genesmentioning

confidence: 99%

The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency

Oleari

Massa

Cariboni

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…New evidence also underlines that genetic investigation cannot be limited to transcribed DNA sequences; intronic or intergenic mutations have recently been associated with the KS phenotype, suggesting that sequence variants located close to exon/intron boundaries should be experimentally investigated for pathogenicity 38 – 40 . Finally, a deletion in a long noncoding RNA, rhabdomyosarcoma 2-associated transcript (RMST), present on chromosome 12, has been identified in a KS patient, another finding that may bring innovative perspectives to the genetic diagnosis of KS 41 .…”

Section: How Many Genes Are Involved In Ks?mentioning

confidence: 99%

“…Although a growing number of genes related to KS are characterised, identifiable disease-causing genetic mutations are currently found in only about 40% of patients. Recent advances in next-generation sequencing technologies, with massively parallel sequencing of multiple samples 42 , and in bioinformatic analysis of the expression, in olfactory or GnRH cells, of genes causative of KS will allow the identification of new factors involved in GnRH neuron biology and in the disease 11 , 40 to be screened for mutations in the remaining 60% of familial and sporadic KS cases, which are still waiting for a diagnostic framework.…”

Section: How Many Genes Are Involved In Ks?mentioning

confidence: 99%

Recent advances in understanding and managing Kallmann syndrome

Swee¹,

Quinton²,

Maggi³

2021

Fac Rev

View full text Add to dashboard Cite

Many of the recent advances in our understanding of human reproductive biology and its genetic basis have arisen directly via the genetic investigation of patients with Kallmann syndrome and their families. The disease is characterised by the association of an isolated defect in the secretion (or, less commonly, action) of gonadotropin-releasing hormone (GnRH) and consequent infertility, with anosmia and potentially other associated non-reproductive features. GnRH-producing neurons are located in the hypothalamic brain region after a peculiar migration during embryonic life. To date, different genes affecting GnRH neuron development/migration have so far been implicated in Kallmann syndrome, but our knowledge of the genetic basis of the syndrome remains incomplete. From a clinical point of view, the disease has suffered from a lack of definitive diagnosis and treatment, and although progress has been made in terms of timely diagnosis and evidence-based treatment of patients, implementation remains inconsistent. These aspects will be discussed in this review, which examines new strategies for arriving at more evidence-based and patient-centred medical practice in Kallmann syndrome.

show abstract

“…In 2015, the European CHH consensus summarized 31 pathogenic genes, including X-chromosome-linked recessive, autosomal recessive, and dominant genes [1]. At present, more than 90 candidate genes may be involved in the pathogenesis of CHH, and some newly reported genes have been con rmed in CHH patients; some genes involved in GnRH neuronal migration and axon formation in animal models have not been con rmed in CHH patients [7,[9][10][11][12][13][14][15]. In our previous study, only 10 pathogenic genes were con rmed in CHH patients [8].…”

Section: Introductionmentioning

confidence: 99%

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

Wang¹,

Qin²,

Fan³

et al. 2021

Preprint

View full text Add to dashboard Cite

BackgroundsCongenital 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. MethodsMedical records of 126 patients with CHH at our hospital during 2008−2020 were evaluated. ResultsTotally, 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). ConclusionMicropenis 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.

show abstract

Identification of ROBO1/2 and SCEL as candidate genes in Kallmann syndrome with emerging bioinformatic analysis

Cited by 9 publications

References 24 publications

The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency

The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency

Recent advances in understanding and managing Kallmann syndrome

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

Contact Info

Product

Resources

About