Familial isolated hyperparathyroidism is linked to a 1.7 Mb region on chromosome 2p13.3-14

Warner, Janet

doi:10.1136/jmg.2005.035766

Cited by 49 publications

(24 citation statements)

References 18 publications

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“…Diseases caused by duplication of individual genes in the region have not been described, and the consequences of the 149 gene duplications are difficult to predict. Familial isolated hyperparathyroidism (FIHP), which is an autosomal dominant inherited form of primary hyperparathyroidism in adults, has been linked to a 1.7-Mb region, which is included in the duplicated region of our patient [22]. In a previous publication, two candidate genes, PPP3R1 and PROKR1 (PKR1) , from the linked region were sequenced in patients with FIHP, but no pathogenic variants were found [22].…”

Section: Discussionmentioning

confidence: 99%

“…Familial isolated hyperparathyroidism (FIHP), which is an autosomal dominant inherited form of primary hyperparathyroidism in adults, has been linked to a 1.7-Mb region, which is included in the duplicated region of our patient [22]. In a previous publication, two candidate genes, PPP3R1 and PROKR1 (PKR1) , from the linked region were sequenced in patients with FIHP, but no pathogenic variants were found [22]. No study on copy number variation in the region has been completed [Frykholm, pers.…”

Section: Discussionmentioning

confidence: 99%

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Hypercalcaemia in a Patient with 2p13.2-p16.1 Duplication

Lodefalk

Frykholm²,

Esbjörner³

et al. 2015

Horm Res Paediatr

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Background: Partial duplication of 2p is a rare condition that causes facial anomalies, psychomotor delay, and growth failure. Hypercalcaemia is rare in children. So far, duplication of 2p has never been associated with hypercalcaemia. Methods: Here, we report a girl with a partial duplication of 2p presenting with moderate to severe hypercalcaemia at the age of 2 years. She also had hypercalciuria, nephrocalcinosis, decreased renal function, and secondary hyperparathyroidism at presentation. She was thoroughly investigated, including genetic testing of the CYP24A1, CASR, ALPL, and NOD2 genes, to determine the cause of hypercalcaemia. Results: 1,25-dihydroxyvitamin D levels were increased. Hypercalcaemia and hypercalciuria responded well to glucocorticoids but not to cinacalcet. Hyperparathyroidism resolved with improving renal function. Apart from the known duplication of 2p, no pathogenic variants were detected in the studied genes. The duplication of 2p contains the PPP3R1 gene, which encodes for the calcineurin B subunit. Conclusion: We conclude that partial duplication of 2p can be associated with hypercalcaemia and hypercalciuria and hypothesise that the underlying mechanism is an increased extra-renal, parathyroid hormone-independent 25-hydroxyvitamin D 1α-hydroxylase activity, leading to raised amounts of 1,25-dihydroxyvitamin D. The increased enzymatic activity could possibly be caused by calcineurin B subunit-related macrophage stimulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hypercalcaemia in a Patient with 2p13.2-p16.1 Duplication

Lodefalk

Frykholm²,

Esbjörner³

et al. 2015

Horm Res Paediatr

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“…They are usually seen in the context of syndromes, such as multiple endocrine neoplasia types 1 and 2 (MEN 1, MIM #131100 and MEN 2, MIM #171400, respectively), hyperparathyroidism-jaw tumor syndrome (HPT-JT, MIM #145001), familial benign hypocalciuric hypercalcemia (FHH, MIM #145980) and familial isolated hyperparathyroidism (FIHP, #145000) (1). FIHP is a rare autosomal dominant condition, characterized by the occurrence of familial hyperparathyroidism in the absence of other associated lesions or endocrinopathies, with a clinical and genetically heterogeneous presentation (2)(3)(4)(5)(6). Most FIHP families do not have identifi able mutations, although some patients have been found to harbor germline mutations in MEN1, CASR, HRPT2 and, more recently, studies have also linked a FIHP locus to chromosome 2p14-p13.3 (HRPT3) (2,3).…”

Section: Introductionmentioning

confidence: 99%

“…FIHP is a rare autosomal dominant condition, characterized by the occurrence of familial hyperparathyroidism in the absence of other associated lesions or endocrinopathies, with a clinical and genetically heterogeneous presentation (2)(3)(4)(5)(6). Most FIHP families do not have identifi able mutations, although some patients have been found to harbor germline mutations in MEN1, CASR, HRPT2 and, more recently, studies have also linked a FIHP locus to chromosome 2p14-p13.3 (HRPT3) (2,3).…”

Section: Introductionmentioning

confidence: 99%

HRPT2-related familial isolated hyperparathyroidism: could molecular studies direct the surgical approach?

Silveira

Dias²,

Marinho³

et al. 2008

Arq Bras Endocrinol Metab

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It is still debatable which is the best management to familial forms of hyperparathyroidism. Conservative, minimally invasive or aggressive surgical approaches have been proposed from different groups around the world. Our objective was to study the gene mutation, expression of HRPT2 and the clinical outcome after 32 years of follow-up in one Brazilian kindred with familial isolated hyperparathyroidism (FIHP). Clinical and biochemical data, direct sequencing of the HRPT2 gene, analysis of parafi bromin expression using RT-PCR, and immunohistochemistry were done. A nonsense mutation was found in exon 1 (c.96G>A)(p.Trp32X) in all affected members studied. Using RT-PCR, mRNA transcription was altered with complete absence of both transcripts in tumor tissue. Immunohistochemical analysis of tumors showed loss of parafi bromin immunoreactivity. In this kindred there was a high prevalence of recurrence (75%), or persistence after less than subtotal parathyroidectomy that led us to consider a more aggressive surgical approach should be discussed among the affected family members, once surgical criteria was met. We concluded that it is necessary to individualize the surgical approach for HRPT2-related hyperparathyroidism until we can gather a better phenotypegenotype correlation in larger series, to best defi ne their treatment. RESUMO Formas Familiares de Hiperparatireoidismo Relacionadas a Mutações no Gene HRPT2: Estudos Moleculares Poderiam Direcionar Procedimentos Cirúrgicos?A melhor conduta nas formas familiares de hiperparatireoidismo relacionadas a mutações no gene HRPT2 ainda é controvertida. Cirurgias conservadoras, minimamente invasivas ou mais agressivas já foram propostas por diferentes grupos. Objetivamos estudar a seqüência e a expressão do gene HRPT2, além do desfecho clínico, após seguimento de até 32 anos de uma família brasileira com hiperparatireodismo familiar isolado (FIHP). Utilizamos dados clínicos e bioquímicos, seqüenciamento direto do HRPT2 além de análise da expressão da parafi bromina através da RT-PCR e imunohistoquímica. Foi identifi cada mutação nonsense no éxon 1 (c.96G>A)(p.Trp32X) em todos os membros afetados que foram estudados. A análise do mRNA transcrito, através da RT-PCR, demonstrou ausência do transcrito no tecido tumoral. A imunohistoquímica também evidenciou ausência da parafi bromina. Nessa família houve alta (75%) prevalência de recorrência ou persistência da doença após paratireoidectomia parcial o que nos levou a considerar fundamental discutir uma abordagem cirúrgica mais agressiva com os outros familiares portadores da mutação caso critérios de indicação cirúrgica sejam atingidos. Dessa maneira, até que estudos mais amplos estabeleçam uma correlação genótipo-fenótipo no hiperparatireoidismo familiar relacionado a mutações no HRPT2, a abordagem cirúrgica deverá ser individualizada. Silveira et al. HRPT2 mutations in FIHP and surgery

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“…After the exclusion of such mutations, the genetic background of familial isolated hyperparathyroidism remains unclear in most of the families. Recently, familial isolated hyperparathyroidism was linked to a 1.7 Mb region on chromosome 2p13.3-14 during a genome-wide screen of DNA from seven families; however, sequencing of the two most likely candidate genes in this region failed to reveal any mutation [30]. Until cloning and sequencing of the putative familial isolated hyperparathyroidism gene(s), the review article 239 diagnosis of this syndrome rests on the exclusion of other specific endocrine and non-endocrine tumors associated with MEN1, MEN2 and HPT-JT syndrome, as well as CaSR mutations.…”

Section: Familial Isolated Hyperparathyroidismmentioning

confidence: 99%

Parathyroid hormone-dependent hypercalcemia

Tőke

Patócs

Balogh

et al. 2009

Wien Klin Wochenschr

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The past fifteen years have resulted in great progress in our understanding of the pathogenesis and pathophysiology of hypercalcemic disorders occurring either sporadically or in a familial setting. This paper briefly reviews the clinically most important new knowledge on sporadic and hereditary forms of parathyroid hormone-dependent hypercalcemic disorders, with special emphasis on familial syndromes such as multiple endocrine neoplasia type 1 and type 2A, hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism, familial hypocalciuric hypercalcemia and neonatal severe primary hyperparathyroidism. In addition, the authors briefly present the most important clinical characteristics of 141 patients with parathyroid hormone-dependent hypercalcemia, including index patients of 18 families with hereditary disorders, diagnosed in a Hungarian endocrine center between 1997 and 2007.

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Familial isolated hyperparathyroidism is linked to a 1.7 Mb region on chromosome 2p13.3-14

Cited by 49 publications

References 18 publications

Hypercalcaemia in a Patient with 2p13.2-p16.1 Duplication

Hypercalcaemia in a Patient with 2p13.2-p16.1 Duplication

HRPT2-related familial isolated hyperparathyroidism: could molecular studies direct the surgical approach?

Parathyroid hormone-dependent hypercalcemia

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