Normosmic idiopathic hypogonadotropic hypogonadism due to a novel homozygous nonsense c.C969A (p.Y323X) mutation in the <i><scp>KISS</scp>1R</i> gene in three unrelated families

Demirbilek, Hüseyin; Özbek, Mehmet Nuri; Demır, Kadir; Kotan, Leman Damla; Cesur, Yaşar; Doğan, Murat; Temiz, Fatih; Mengen, Eda; Gürbüz, Fatih; Yüksel, Bilgin; Topaloğlu, Ali Kemal

doi:10.1111/cen.12618

Cited by 20 publications

(18 citation statements)

References 34 publications

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“…They had a UBE3B frameshift deletion, creating a stop codon in exon 17, expected to result in a transcript lacking the catalytic HECT domain. Frameshift mutations usually lead to nonsense meditated decay, however the UBE3B transcript levels in the patients and parents were similar to healthy controls, likely as a result of nonsense mediated decay escape mechanism [Zhang and Maquat, ; Nagy and Maquat, ; Demirbilek et al, ; Symoens et al, ]. The mutation causing an altered translation initiation codon might lead to the use of an in‐frame downstream ATG as start codon (N‐terminal truncation).…”

Section: Discussionmentioning

confidence: 99%

Kaufman oculocerebrofacial syndrome in sisters with novel compound heterozygous mutation in UBE3B

Pedurupillay

Barøy

Holmgren

et al. 2015

American J of Med Genetics Pt A

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A pair of sisters was ascertained for multiple congenital defects, including marked craniofacial dysmorphisms with blepharophimosis, and severe psychomotor delay. Two novel compound heterozygous mutations in UBE3B were identified in both the sisters by exome sequencing. These mutations include c.1A>G, which predicts p.Met1?, and a c.1773delC variant, predicted to cause a frameshift at p.Phe591fs. UBE3B encodes a widely expressed protein ubiquitin ligase E3B, which, when mutated in both alleles, causes Kaufman oculocerebrofacial syndrome. We report on the thorough clinical examination of the patients and review the state of art knowledge of this disorder.

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Section: Discussionmentioning

confidence: 99%

Kaufman oculocerebrofacial syndrome in sisters with novel compound heterozygous mutation in UBE3B

Pedurupillay

Barøy

Holmgren

et al. 2015

American J of Med Genetics Pt A

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“…14 A few genes that are involved in the pathogenesis of IHH have been identified at various sites, including TAC3, TACR3, GnRHR, FGFR1, GNRH1, FGF8, KISS1, and KISS1R. 11 However, these genetic defects account for less than 30% of patients with IHH. 15 AR AURKC CATSPER1 CCDC39 CFTR CHD7 DNAAF1 DNAAF2 DNAAF3 DNAH1 DNAH11 DNAH5 DNAI1 DNAI2 DPY19L2 DYX1C1 ETV5 FGF8 FGFR1 GNRHR HEATR2 HSF2 HYDIN KAL1 KISS1R LEP LEPR NANOS1 NELF NR5A1 PLCZ1 PROK2 PROKR2 RHOXF1 RHOXF2 RSPH1 RSPH4A RSPH9 SEPT12 SLC26A8 SOHLH2 SPATA16 SUN5 SYCE1 SYCP3 TAC3 TACR3 TEX11 USP26 WDR11 ZMYDN15 In previous studies, KISS1R was one of the major genes that implicated in IHH in the autosomal-recessive form.…”

Section: Discussionmentioning

confidence: 99%

Identification of KISS1R gene mutations in disorders of non‐obstructive azoospermia in the northeast population of China

Geng

Zhang

Liu

et al. 2019

Clinical Laboratory Analysis

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Background: Non-obstructive azoospermia (NOA), a serious phenotype of male spermatogenesis failure, is a multifactorial disease which is regulated by genetic, epigenetic, and environmental factors. Some gene structural variants have been demonstrated to be related to NOA. Loss-of-function mutations of KISS1R cause normosmic idiopathic hypogonadotropic hypogonadism (IHH) which result in azoospermia at the pre-testicular level. The objective of this research was to investigate genetic variants of KISS1R in NOA patients. Methods:The entire coding region of 52 spermatogenesis-associated genes (KISS1R included) was sequenced from 200 NOA patients. Mutation screening was performed to identify genetic variations of these genes by targeted exome sequencing. Sequencing data analysis was carried out by a series of bioinformatics tools.Candidate variants confirmation was performed by Sanger sequencing. Functional analysis of candidate variants was evaluated using SIFT and PolyPhen-2.Results: Three heterozygous missense variants in KISS1R were identified in three patients, respectively. No deleterious variations in other candidate genes were found in the three patients. Two of these three variants, p.A211T and p.G186E, had been reported in the ExAC and dbSNP database, respectively, while the other variant p.A301D was novel. These variants were all predicted to be likely pathogenic by in silico analysis. Conclusion:Our study revealed three heterozygous missense variants in KISS1R which expanded the mutation spectrum of KISS1R in infertile men with NOA in the northeast of China.

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“…The scarcity of genetic data in patients with IHH makes it difficult to genetically characterize this condition. However, more recently, another type of loss-of-function mutation of the KISS1R gene was newly discovered in three unrelated Kurdish families ( 12 ). This was a nonsense c.C969A (Y323X) mutation.…”

Section: Discussionmentioning

confidence: 99%

“…Other types of gene mutations have been found in Kurdish families ( 12 ). The Kurdish population are descendants of a small number of ancestors, and there is a high prevalence of consanguinity among them, resulting in over-dominant selection of heterozygous carriers and homozygous offspring with deleterious gene mutations such as the GPR54 gene mutation in this case.…”

Section: Discussionmentioning

confidence: 99%

Normosmic idiopathic hypogonadotrophic hypogonadism due to a rare KISS1R gene mutation

Chelaghma

Oyibo

Rajkanna

2018

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryHypogonadotrophic hypogonadism is due to impaired or reduced gonadotrophin secretion from the pituitary gland. In the absence of any anatomical or functional lesions of the pituitary or hypothalamic gland, the hypogonadotrophic hypogonadism is referred to as idiopathic hypogonadotrophic hypogonadism (IHH). We present a case of a young lady born to consanguineous parents who was found to have IHH due to a rare gene mutation.Learning points:The genetic basis of a majority of cases of IHH remains unknown.IHH can have different clinical endocrine manifestations.Patients can present late to the healthcare service because of unawareness and stigmata associated with the clinical features.Family members of affected individuals can be affected to varying degrees.

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Normosmic idiopathic hypogonadotropic hypogonadism due to a novel homozygous nonsense c.C969A (p.Y323X) mutation in the KISS1R gene in three unrelated families

Cited by 20 publications

References 34 publications

Kaufman oculocerebrofacial syndrome in sisters with novel compound heterozygous mutation in UBE3B

Kaufman oculocerebrofacial syndrome in sisters with novel compound heterozygous mutation in UBE3B

Identification of KISS1R gene mutations in disorders of non‐obstructive azoospermia in the northeast population of China

Normosmic idiopathic hypogonadotrophic hypogonadism due to a rare KISS1R gene mutation

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