Genetic Etiology of Idiopathic Hypogonadotropic Hypogonadism

Topaloğlu, Ali Kemal; Turan, İhsan

doi:10.3390/endocrines3010001

Cited by 7 publications

(11 citation statements)

References 107 publications

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“…IHH is a rare disease characterized by pubertal failure and infertility, with a prevalence of 1/10-100.000 ( 10 ). Mutations detected in patients with IHH, based on the Mendelian inheritance model, are currently thought to be responsible for approximately 50% of all cases ( 11 ).…”

Section: Methodsmentioning

confidence: 99%

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Comparative Analyses of Turkish Variome and Widely Used Genomic Variation Databases for the Evaluation of Rare Sequence Variants in Turkish Individuals: Idiopathic Hypogonadotropic Hypogonadism as a Disease Model

Kotan

2022

Jcrpe

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Objective: With the increasing use of whole-exome sequencing, one of the challenges in identifying the causal allele for a Mendelian disease is the lack of availability of population-specific human genetic variation reference databases. The people of Turkey were not represented in GnomAD or other publicly available large databases until recently, when the first comprehensive genomic variation database, Turkish Variome (TRV), was published. The aim of this study was to evaluate whether TRV or other publicly available large genomic variation databases can reliably be used for rare disease variant evaluation in Turkish individuals. Methods: Sixty non-disease-causing, non-synonymous variants (minor allele frequencies >1%) were identified in 58 genes that are known to be associated with idiopathic hypogonadotropic hypogonadism from a large Turkish patient cohort. The allelic frequencies of these variants were then compared with those in various public genomic variation databases, including TRV. Results: Our cohort variants showed the highest correlations with those in the TRV, Iranome, and The Greater Middle East Variome, in decreasing order. Conclusion: These results suggest that the TRV is the appropriate database to use for rare genomic variant evaluations in the Turkish population. Our data also suggest that variomes from geographic neighborhoods may serve as substitute references for populations devoid of their own genomic variation databases.

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Section: Methodsmentioning

confidence: 99%

“…Intronic areas, distant regions, and synonymous changes were excluded. Currently known-IHH-associated genes are listed in Table 1 ( 11 ).…”

Section: Methodsmentioning

confidence: 99%

Comparative Analyses of Turkish Variome and Widely Used Genomic Variation Databases for the Evaluation of Rare Sequence Variants in Turkish Individuals: Idiopathic Hypogonadotropic Hypogonadism as a Disease Model

Kotan

2022

Jcrpe

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“…Therefore, the genes reported for KS and normosmic HH were screened in the patient's WES data. HH‐related 62 genes and HUGO Gene Nomenclature Committee IDs are as follows: AMH (464), AMHR2 (465), AXL (905), DCC (2701), DLG2 (2901), DMXL2 (2938), DUSP6 (3072), FGF17 (3673), FGF8 (3686), FGFR1 (3688), FLRT3 (3762), FSHB (3964), GNRH1 (4419), GNRHR (4421), KISS1R (4510), HESX1 (4877), HS6ST1 (5201), ANOS1 (6211), KISS1 (6341), LEP (6553), LEPR (6554), LHB (6584), NHLH2 (7818), NR0B1 (7960), NTN1 (8029), PCSK1 (8743), PLXNA1 (9099), PLXNA3 (9101), PLXNB1 (9103), SEMA3A (10723), SEMA3E (10727), SEMA3F (10728), SOX10 (11190), SOX3 (11199), SRA1 (11281), STUB1 (11427), RAB18 (14244), TAC3 (11521), TACR3 (11528), TCF12 (11623), WDR11 (13831), KLB (15527), SPRY4 (15533), PROKR2 (15836), TBC1D20 (16133), PNPLA6 (16268), RAB3GAP1 (17063), RAB3GAP2 (17168), IL17RD (17616), PROK2 (18455), CHD7 (20626), TUBB3 (20772), RNF216 (21698), FEZF1 (22788), OTUD4 (24949), NDNF (26256), IGSF10 (26384), CCDC141 (26821), SMCHD1 (29090), NSMF (29843), POLR3A (30074), and POLR3B (30348) (Topaloglu & Turan, 2022).…”

Section: Methodsmentioning

confidence: 99%

“…It is estimated that about half of hereditary cases can be explained by a genetic background that includes more than 50 genes. (Topaloglu & Turan, 2022).…”

Section: Introductionmentioning

confidence: 99%

A novel homozygous nonsense NDNF variant in Kallmann syndrome

Kotan

Yildiz

Turan

et al. 2022

American J of Med Genetics Pt A

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Kallmann syndrome (KS) is a rare genetic disease characterized by pubertal failure and olfactory defects. Although many genes associated with KS have been reported, most are rare. Recently, heterozygous inactivating mutations in the neuron‐derived neurotrophic factor gene (NDNF) were reported to cause KS. Here, we present a 14‐year‐old Kurdish boy with KS who has a novel homozygous nonsense c.1251C>A (p.Tyr417Ter) variant in NDNF. The variant was not observed in reference population databases and was predicted to be deleterious. Segregation analysis performed with Sanger sequencing indicated the autosomal recessive inheritance of the clinical phenotype. His heterozygous parents have experienced timely pubertal development and normal reproductive features. This study reported the first homozygous truncating NDNF variant, enabling the direct observation of the clinical consequences of predictively absent NDNF function. These results support the contention that the inactivating mutations in NDNF cause KS, and provide additional evidence for the complex inheritance of KS.

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“…2 Congenital central nervous system (CNS) lesions (Chiari malformation, hydrocephalus, arachnoid cyst, hypothalamic hamartoma, myelomeningocele), acquired CNS lesions (tumors such as glioma, ependymoma, pinealoma and craniopharyngioma, hypoxic ischemic encephalopathy, irradiation, traumatic injury, bleeding, infection), genetic mutations, chromosomal abnormalities and idiopathic precocious puberty are among the causes of central precocious puberty. 3,4 Th e control mechanisms that onset puberty are still undiscovered. Th e phenomenon that induces puberty is thought to be an increase in the amplitude and quantity of GnRH secretory bursts by the hypothalamic neurons that produce GnRH.…”

Section: Introductionmentioning

confidence: 99%

Erken puberte tanılı olgularda epifiz kistleri: Tesadüfi bir bulgu mu?

Ciraci

Polat

2022

Sakarya Medical Journal

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Amaç: Bu çalışmanın amacı, çocuklarda erken puberte ile pineal kistler arasındaki ilişkinin değerlendirilmesidir. Gereç ve Yöntemler: Erken puberte tanılı 122 olgu ve 122 kontrol grubu çocuğun beyin MR görüntüleri pineal kist varlığı ve boyutları açısından değerlendirildi. Pineal kistler boyutlarına göre gerçek kist ve kistik transformasyon olarak değerlendirildi. Erken puberte ve kontrol grubu pineal kist/kistik transformasyon varlığı açısından karşılaştırıldı. Erken puberte grubunda pineal kist saptanan, kistik transformasyon saptanan ve kist/kistik transformasyon saptanmayanların pik ve bazal LH değerleri karşılaştırıldı. Bulgular: Ki-kare testi ile erken puberte ile pineal kist arasında ve erken puberte ile pineal kistik transformasyon arasında anlamlı ilişki saptanmadı (sırasıyla p=0,2537ve p=0,8797). Erken puberte grubunda kist/kistik transformasyon izlenmeyen, kistik transformasyon saptanan ve kist saptananlar arasında pik ve bazal LH değerleri açısından anlamlı farklılık bulunmadı (sırasıyla p=0,566 ve p=0,367). Sonuç: Çalışmamızın sonuçlarına göre , pineal kistler ile erken puberte arasında herhangi bir ilişki saptanmamıştır. Bu nedenle, erken puberte tanılı olgularda MR incelemelerde saptanan pineal kistlerin insidental bulgu olarak kabul edilmeleri doğru bir yaklaşımdır.

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Genetic Etiology of Idiopathic Hypogonadotropic Hypogonadism

Cited by 7 publications

References 107 publications

Comparative Analyses of Turkish Variome and Widely Used Genomic Variation Databases for the Evaluation of Rare Sequence Variants in Turkish Individuals: Idiopathic Hypogonadotropic Hypogonadism as a Disease Model

Comparative Analyses of Turkish Variome and Widely Used Genomic Variation Databases for the Evaluation of Rare Sequence Variants in Turkish Individuals: Idiopathic Hypogonadotropic Hypogonadism as a Disease Model

A novel homozygous nonsense NDNF variant in Kallmann syndrome

Erken puberte tanılı olgularda epifiz kistleri: Tesadüfi bir bulgu mu?

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