Clinical utility gene card for: poikiloderma with neutropenia

Larizza, Lidia; Negri, Gloria; Colombo, E.; Volpi, L.; Sznajer, Yves

doi:10.1038/ejhg.2012.298

Cited by 9 publications

(6 citation statements)

References 18 publications

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“…PN has two hallmarks: “poikiloderma” and mild to severe “neutropenia”. The latter predisposes to myelodysplasia and acute myeloid leukaemia 3 4 5 6 12 13 thus featuring PN as a disorder of the haematopoietic cascade, mainly of the myeloid lineage. Biochemical studies on yeast and lymphoblastoid cells from PN patients have shown that USB1 plays a crucial role in the stability and recycling of U6 snRNA, a component of the RNA splicing machinery 16 17 18 .…”

Section: Discussionmentioning

confidence: 99%

“…Discovery of the causative C16orf57 gene by autozygosity mapping and next-generation sequencing of the linkage region on chromosome 16 6 , confirmed that PN is genetically distinct from clinically overlapping entities, in particular Rothmund-Thomson syndrome (OMIM#268400), and allowed the introduction of the genetic test to validate diagnosis and provide patients with the appropriate oncological surveillance 7 8 9 10 11 . Neutropenia, the distinctive PN hallmark, confers on patients a high risk to develop myelodysplasia, often evolving into acute myeloid leukaemia in the second decade of life 12 13 .…”

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confidence: 99%

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A zebrafish model of Poikiloderma with Neutropenia recapitulates the human syndrome hallmarks and traces back neutropenia to the myeloid progenitor

Colombo

Carra

Fontana

et al. 2015

Sci Rep

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Poikiloderma with Neutropenia (PN) is an autosomal recessive genodermatosis characterized by early-onset poikiloderma, pachyonychia, hyperkeratosis, bone anomalies and neutropenia, predisposing to myelodysplasia. The causative C16orf57/USB1 gene encodes a conserved phosphodiesterase that regulates the stability of spliceosomal U6-RNA. The involvement of USB1 in splicing has not yet allowed to unveil the pathogenesis of PN and how the gene defects impact on skin and bone tissues besides than on the haematological compartment. We established a zebrafish model of PN using a morpholino-knockdown approach with two different splicing morpholinos. Both usb1-depleted embryos displayed developmental abnormalities recapitulating the signs of the human syndrome. Besides the pigmentation and osteochondral defects, usb1-knockdown caused defects in circulation, manifested by a reduced number of circulating cells. The overall morphant phenotype was also obtained by co-injecting sub-phenotypic dosages of the two morpholinos and could be rescued by human USB1 RNA. Integrated in situ and real-time expression analyses of stage-specific markers highlighted defects of primitive haematopoiesis and traced back the dramatic reduction in neutrophil myeloperoxidase to the myeloid progenitors showing down-regulated pu.1 expression. Our vertebrate model of PN demonstrates the intrinsic requirement of usb1 in haematopoiesis and highlights PN as a disorder of myeloid progenitors associated with bone marrow dysfunction.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A zebrafish model of Poikiloderma with Neutropenia recapitulates the human syndrome hallmarks and traces back neutropenia to the myeloid progenitor

Colombo

Carra

Fontana

et al. 2015

Sci Rep

Self Cite

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“…Before treatment, his length was 132 cm (−3.8 SD) and his final length was 156 cm (−3.5 SD). To our knowledge, this is the first patient that GH therapy is applied for a PN patient [Larizza et al, ]. To demonstrate the effects of the GH therapy, further practices are needed.…”

Section: Discussionmentioning

confidence: 99%

Poikiloderma with neutropenia: Genotype‐ethnic origin correlation, expanding phenotype and literature review

Koparır

Gezdirici

Koparir

et al. 2014

American J of Med Genetics Pt A

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Poikiloderma with neutropenia (PN), is a rare genodermatosis associated with patognomic features of poikiloderma and permanent neutropenia. Three common recurrent mutations of related gene, USB1, were considered to be associated with three different ethnic origins. The most common recurrent mutation, c.531delA, has been detected in seven Caucasian patients in the literature. In this paper, we present review of all patients from the literature and report two additional patients of Turkish ancestry with the diagnosis of PN. The diagnosis of these two PN patients were made clinically and confirmed by molecular analysis which detected the most common recurrent mutation, c.531delA. Genotype-ethnic origin correlation hypothesis, therefore, has been strengthened with this result. Short stature in PN, is a common finding, which until now has never been treated with growth hormone (GH). One of our patients is the first patient with attempted treatment of short stature via GH administration. Finally, both of our patients had high-pitched voice and vocal cord nodules which might be considered as additional clinical findings not associated with PN before.

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“…2,7 The identification of a molecular anomaly in FAM111B gives definitive proof of POIKTMP and enables its distinction from other types of hereditary poikiloderma, such as RTS (MIM#268400), hereditary sclerosing poikiloderma of Weary (MIM#173700), poikiloderma with neutropenia (PN; MIM#604173) or Kindler syndrome (MIM#173650). 6,[8][9][10][11] Above all, the main differential diagnosis of POIKTMP is RTS as all patients were initially misdiagnosed with RTS in childhood. These two entities share indeed common characteristics, such as early-onset poikiloderma, ectodermal dysplasia features, palmoplantar hyperkeratotic lesions, growth delay.…”

Section: Diagnostic Settingmentioning

confidence: 99%

CUGC for hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP)

et al. 2015

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Clinical utility gene card for: poikiloderma with neutropenia

Cited by 9 publications

References 18 publications

A zebrafish model of Poikiloderma with Neutropenia recapitulates the human syndrome hallmarks and traces back neutropenia to the myeloid progenitor

A zebrafish model of Poikiloderma with Neutropenia recapitulates the human syndrome hallmarks and traces back neutropenia to the myeloid progenitor

Poikiloderma with neutropenia: Genotype‐ethnic origin correlation, expanding phenotype and literature review

CUGC for hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP)

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