Similar interstitial deletions of the KAL-1 gene in two Brazilian families with X-linked Kallmann Syndrome

Trarbach, Ericka Barbosa; Monlleó, Isabella Lopes; Fontes, Marshall Ítalo Barros; Baptista, Mónica; Hackel, Christine

doi:10.1590/s1415-47572004000300006

Cited by 9 publications

(5 citation statements)

References 31 publications

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“…Among the 21 KS patients who underwent renal ultrasound, seven (30%) had a kidney abnormality 19,31,43 and renal aplasia was found in three patients with an X‐linked inheritance pattern. Although renal aplasia is commonly found in X‐linked KS patients, it was recently described in a sporadic case of KS with no KAL1 mutation 19 .…”

Section: Discussionmentioning

confidence: 99%

Clinical assessment and molecular analysis of GnRHR and KAL1 genes in males with idiopathic hypogonadotrophic hypogonadism

Versiani¹,

Trarbach

Koenigkam-Santos

et al. 2006

Clinical Endocrinology

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Section: Discussionmentioning

confidence: 99%

Clinical assessment and molecular analysis of GnRHR and KAL1 genes in males with idiopathic hypogonadotrophic hypogonadism

Versiani¹,

Trarbach

Koenigkam-Santos

et al. 2006

Clinical Endocrinology

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“…We have previously identified three other KAL-1 abnormalities in this series of Brazilian KS patients: in a sporadic case (KS1) a KAL-1 gene microdeletion was detected by fluorescence in situ hybridization, while in two families with X-linked inheritance (patients KS2 and KS7) similar intragenic deletions of exons 5-10 were found after PCR analysis (Trarbach et al 2001(Trarbach et al , 2004. Thus, the prevalence of KAL1 mutations in these Brazilian patients was 100% in the familial X-linked KS (three of three families) and 30% in sporadic cases (two of seven).…”

Section: Discussionmentioning

confidence: 84%

“…Molecular analysis of the KAL-1 gene was initially carried out both in KS and nHH patients; exceptions were made for the three KS patients (KS1, KS2 and KS7) in which genotypes have been previously described (Trarbach et al 2001(Trarbach et al , 2004. The five nHH patients were further screened for mutations in the GnRH-R gene.…”

Section: Methodsmentioning

confidence: 99%

Molecular analysis of KAL-1, GnRH-R, NELF and EBF2 genes in a series of Kallmann syndrome and normosmic hypogonadotropic hypogonadism patients

Trarbach¹,

Baptista²,

Garmes³

et al. 2005

Journal of Endocrinology

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We report the results of molecular analysis in a series of twelve Kallmann syndrome (KS) and five normosmic hypogonadotropic hypogonadism (nHH) Brazilian patients. Kallman syndrome 1 (KAL-1) gene analysis was performed in all patients and the gonadotrophin releasing hormone receptor (GnRH-R) gene was investigated in nHH patients using PCR analysis with exon-flanking primers followed by automated sequencing techniques. Two-point mutations at the KAL-1 locus were found in two KS patients. One case exhibited a novel C deletion (del1956C) in exon 12 leading to a premature stop codon at position 617. The second case, a C to T transition at exon 5, showed a stop codon at aminoacid 191 (Arg191X). Renal agenesis and bimanual synkinesis, which are frequently found in patients with the KAL-1 mutation, were observed in these cases. Among the KS patients, two previously reported cases had intragenic deletions of exons 5-10, while a third patient had a KAL-1 gene microdeletion detected by fluorescence in situ hybridization. For the nHH patients, no abnormalities were observed at the exonic and flanking sequences of the KAL-1 or GnRH-R genes. Nasal embryonic LHRH factor (NELF) and early B-cell factor 2 (EBF2) exons were evaluated in KAL-1/GnRH-R mutation-negative cases (seven KS and five nHH) by sequence analysis but no mutations were identified in the coding regions in these patients. In conclusion, this report includes the description of a novel point mutation of the KAL-1 gene and suggests that the KAL-1 mutations and deletions might be more prevalent in KS Brazilian patients than previously described in other series. NELF and EBF2 genes have been considered good candidates for HH and a large number of patients need to be studied to assess their contribution to reproductive function.

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“…Renal agenesis is the most common complication for KS patients, which may provide clues for the early diagnosis and treatment of the patient. Fourteen types of urinary disorders in the KS patients have been reported before, including renal agenesis (unilateral and bilateral), [ 4 ] renal malrotation, [ 8 ] bilateral dilatation of the calyces and pelves, [ 8 ] horseshoe kidneys, [ 9 ] multicystic dysplastic kidneys, [ 10 ] vesiculourateral reflux, [ 10 , 11 ] ectopic right ureteric orifice, [ 12 ] left hydronephrosis, [ 11 ] left reflux [ 11 ] and hyderoureter. [ 11 ] In this case, we reported 8 rare urinary disorders co-exist in one patient, in which bilateral giant kidneys, urinary extravasation of right renal, bilateral megalo-ureters, left ureteral terminal obstruction, bilateral renal cyst and bladder emptying disorder have not been reported before.…”

Section: Discussionmentioning

confidence: 99%

Eight rare urinary disorders in a patient with Kallmann syndrome

Tian

et al. 2020

Medicine

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Rationale: Kallmann syndrome (KS) is a rare inherited genetic disorder characterized by hypogonadotropic hypogonadism and hyposmia/anosmia. Early diagnosis is the key to timely treatment and improvement of prognosis in patients with KS. As the most common complication of KS, renal agenesis can provide clues to early diagnosis and treatment for KS. In this article, we report a case of KS with 8 rare urinary disorders for the first time. Patient concerns: A 19-year-old Chinese man presented with 8 rare urinary disorders and a history of bilateral cryptorchidism came to us for micropenis, hyposmia, and delayed puberty. Diagnosis: The patient presented with hyposmia, low levels of sex hormones and showed a weak response to the GnRH stimulation test leading to a diagnosis of KS. Two missense mutations were found in further whole-exome sequencing: 1) Kallmann syndrome 1 ( KAL1 ) gene in exon11, c.1600G > A, p. Val534Ile; 2) Prokineticin receptor 2 ( PROKR2 ) gene in exon 2, c.533G > A, p. Trp178Ser. which led to a diagnosis of KS. Interventions: The patient underwent replacement therapy of human chorionic gonadotropin (HCG) and human menopausal gonadotropin (HMG). The patient had previously undergone six surgeries for cryptorchidism and urinary disorders. Outcomes: The patient's puberty retardation was effectively alleviated. His serum testosterone (T) reached a normal level (8.280 nmol/mL). During the follow-up period, he presented with Tanner stage II pubic hair development. Conclusion: In this article, we report 8 rare urinary disorders with missense mutations of KAL1 and PROKR2 in a case of KS. Among them, bilateral giant kidneys, urinary extravasation of right renal, bilateral megalo-ureters, left ureteral terminal obstruction, bilateral renal cyst and bladder emptying disorder are reported for the first time, which enrich the integrity of urinary disorder types and provide clues to genetic counseling in patients with KS.

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Similar interstitial deletions of the KAL-1 gene in two Brazilian families with X-linked Kallmann Syndrome

Cited by 9 publications

References 31 publications

Clinical assessment and molecular analysis of GnRHR and KAL1 genes in males with idiopathic hypogonadotrophic hypogonadism

Clinical assessment and molecular analysis of GnRHR and KAL1 genes in males with idiopathic hypogonadotrophic hypogonadism

Molecular analysis of KAL-1, GnRH-R, NELF and EBF2 genes in a series of Kallmann syndrome and normosmic hypogonadotropic hypogonadism patients

Eight rare urinary disorders in a patient with Kallmann syndrome

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