Pulmonary fibrosis associated with<i>TINF2</i>gene mutation: is somatic reversion required?

Kannengiesser, Caroline; Borie, Raphaël; Revy, Patrick

doi:10.1183/09031936.00038714

Cited by 14 publications

(13 citation statements)

References 6 publications

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“…40 In addition to mutations in TERT and TERC , rare variants in DKC1 , which encodes the telomerase complex component dyskerin, have recently been described in patients with FIP 45 46. Pulmonary fibrosis has been also identified in families with DC associated with mutations in TINF2 47 48…”

Section: Introductionmentioning

confidence: 99%

Genetics of idiopathic pulmonary fibrosis: from mechanistic pathways to personalised medicine

Spagnolo

Cottin

2016

J Med Genet

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Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and ultimately fatal disorder for which there is no cure. While the disease is by definition idiopathic, accumulating evidence, including familial aggregation of cases and the occurrence of pulmonary fibrosis in the context of a number of rare genetic disorders, indicates that genetic factors contribute significantly to the pathogenesis of IPF. Several disease-associated genetic variants, both rare and common, have been identified in familial and sporadic IPF. While the full clinical implications of these genetic associations remain to be elucidated, observational studies suggest that genotype influences the development of the disease and its outcome. Available data indicate that genetics has the potential to identify individuals at risk of IPF, classify patients more precisely, clarify the key pathways involved in disease pathogenesis and eventually develop more effective targeted therapies. Considerable research is required before a comprehensive disease fingerprint of IPF can be delivered. Nevertheless, the application of rapidly evolving molecular biology and genomic technologies combined with appropriate bioinformatic methodology offers an unprecedented and realistic opportunity to achieve this goal.

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Section: Introductionmentioning

confidence: 99%

Genetics of idiopathic pulmonary fibrosis: from mechanistic pathways to personalised medicine

Spagnolo

Cottin

2016

J Med Genet

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“…Mutations in DKC1, NAF1 and TINF2 are much rarer (figure 1) [9,23,[28][29][30][31][32][33][34][35]. TERT or TERC mutations may be found in about 1-3% of sporadic IPF cases [28].…”

Section: Asymptomatic Involvementmentioning

confidence: 99%

Management of suspected monogenic lung fibrosis in a specialised centre

et al. 2017

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At least 10% of patients with interstitial lung disease present monogenic lung fibrosis suspected on familial aggregation of pulmonary fibrosis, specific syndromes or early age of diagnosis. Approximately 25% of families have an identified mutation in genes mostly involved in telomere homeostasis, and more rarely in surfactant homeostasis.Beyond pathophysiological knowledge, detection of these mutations has practical consequence for patients. For instance, mutations involved in telomere homeostasis are associated with haematological complications after lung transplantation and may require adapted immunosuppression. Moreover, relatives may benefit from a clinical and genetic evaluation that should be specifically managed.The field of genetics of pulmonary fibrosis has made great progress in the last 10 years, raising specific problems that should be addressed by a specialised team.

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“…Sanger sequencing of a cloned segment of PCR amplified DNA encompassing the DC cluster revealed a deletion of nucleotides 871-874, resulting in a frameshift mutation, TIN2p.R291Ifs11X. Because the patient did not develop severe bone marrow failure during the first decade of life, as typically observed in patients carrying a mutation in TINF2, it was suggested subsequently that perhaps she experienced somatic mosaicism, with reversion of the mutant TINF2 allele in some of the peripheral blood cells, thereby, attenuating the bone marrow phenotype 123 . The mosaicism might have been missed by sequence analysis of the cloned PCR fragment.…”

Section: Class V: Multifactorialmentioning

confidence: 98%

The molecular genetics of the telomere biology disorders

2016

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The importance of telomere function for human health is exemplified by a collection of Mendelian disorders referred to as the telomere biology disorders (TBDs), telomeropathies, or syndromes of telomere shortening. Collectively, the TBDs cover a spectrum of conditions from multisystem disease presenting in infancy to isolated disease presentations in adulthood, most notably idiopathic pulmonary fibrosis. Eleven genes have been found mutated in the TBDs to date, each of which is linked to some aspect of telomere maintenance. This review summarizes the molecular defects that result from mutations in these genes, highlighting recent advances, including the addition of PARN to the TBD gene family and the discovery of heterozygous mutations in RTEL1 as a cause of familial pulmonary fibrosis.

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Pulmonary fibrosis associated withTINF2gene mutation: is somatic reversion required?

Cited by 14 publications

References 6 publications

Genetics of idiopathic pulmonary fibrosis: from mechanistic pathways to personalised medicine

Genetics of idiopathic pulmonary fibrosis: from mechanistic pathways to personalised medicine

Management of suspected monogenic lung fibrosis in a specialised centre

The molecular genetics of the telomere biology disorders

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