Journal of Clinical Immunology

, Volume 38, Issue 4, pp 494–502 | Cite as

Insights into Mutation Effect in Three Poikiloderma with Neutropenia Patients by Transcript Analysis and Disease Evolution of Reported Patients with the Same Pathogenic Variants

  • Elisa A. Colombo
  • Nursel H. Elcioglu
  • Claudio Graziano
  • Pamela Farinelli
  • Elisabetta Di Fede
  • Iria Neri
  • Elena Facchini
  • Mariangela Greco
  • Cristina Gervasini
  • Lidia Larizza
Original Article



Poikiloderma with neutropenia (PN) is a genodermatosis currently described in 77 patients, all presenting with early-onset poikiloderma, neutropenia, and several additional signs. Biallelic loss-of-function mutations in USB1 gene are detected in all molecularly tested patients but genotype-phenotype correlation remains elusive. Cancer predisposition is recognized among PN features and pathogenic variants found in patients who developed early in life myelodysplasia (n = 12), acute myeloid leukemia (n = 2), and squamous cell carcinoma (n = 2) should be kept into account in management and follow-up of novel patients. This will hopefully allow achieving data clustered on specific mutations relevant to oncological surveillance of the carrier patients.


We describe the clinical features of three unreported PN patients and characterize their USB1 pathogenic variants by transcript analysis to get insights into the effect on the overall phenotype and disease evolution.


A Turkish boy is homozygous for the c.531delA deletion, a recurrent mutation in Turkey; an adult Italian male is compound heterozygous for two nonsense mutations, c.243G>A and c.541C>T, while an Italian boy is homozygous for the splicing c.683_693+1del variant. The identified mutations have already been reported in PN patients who developed hematologic or skin cancer. Aberrant mRNAs of all four mutated alleles could be identified confirming that transcripts of USB1 main isoform either carrying stop codons or mis-spliced may at least partially escape nonsense-mediated decay.


Our study addresses the need of gathering insights on genotype-phenotype correlations in newly described PN patients, by transcript analysis and information on disease evolution of reported patients with the same pathogenic variants.


Poikiloderma with neutropenia USB1 transcript analysis disease phenotype cancer predisposition 



We thank the patients and their families for their kind participation in this study.

Authorship Contributions

EAC interpreted the molecular results, drafted, revised, and approved the final version; NHE contributed with clinical data and biological samples of family no. #32, drafted the clinical paragraph, and approved the final version; CG contributed with clinical data and biological samples of family no. #49, drafted the clinical paragraph, and approved the final version; PF contributed with clinical data and biological samples of family no. #48, drafted the clinical paragraph, and approved the final version; EDF performed molecular analyses; IN contributed with clinical data and biological samples of family no. #49, drafted the clinical paragraph, and approved the final version; EF contributed with clinical data and biological samples of family no. #49, drafted the clinical paragraph, and approved the final version; MG contributed with clinical data and biological samples of family no. #48, drafted the clinical paragraph, and approved the final version; CG supported the molecular work and software access; LL conceived and coordinated the study, and drafted, revised, and approved the final version of the manuscript.

Funding Information

This work was supported by Italian Ministry of Health to Istituto Auxologico Italiano (LL- Ricerca Corrente 08C624).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no competing interests.

Supplementary material

10875_2018_508_MOESM1_ESM.pdf (278 kb)
ESM 1 (PDF 277 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Elisa A. Colombo
    • 1
  • Nursel H. Elcioglu
    • 2
    • 3
  • Claudio Graziano
    • 4
  • Pamela Farinelli
    • 5
  • Elisabetta Di Fede
    • 1
  • Iria Neri
    • 6
  • Elena Facchini
    • 7
  • Mariangela Greco
    • 8
  • Cristina Gervasini
    • 1
  • Lidia Larizza
    • 9
  1. 1.Dipartimento di Scienze della SaluteUniversità degli Studi di MilanoMilanItaly
  2. 2.Department of Pediatric GeneticsMarmara University Medical SchoolIstanbulTurkey
  3. 3.Department of Pediatric GeneticsTurkey and Eastern Mediterranean UniversityMersinTurkey
  4. 4.U.O. Genetica MedicaPoliclinico S. Orsola-MalpighiBolognaItaly
  5. 5.Clinica DermatologicaAzienda ospedaliero universitaria “Maggiore della Carità”NovaraItaly
  6. 6.U.O. DermatologiaPoliclinico S. Orsola-MalpighiBolognaItaly
  7. 7.U.O. Pediatria - Programma di Oncologia, Ematologia e TrapiantoPoliclinico S. Orsola-MalpighiBolognaItaly
  8. 8.Divisione di EmatologiaAzienda Ospedaliero Universitaria “Maggiore della Carità”NovaraItaly
  9. 9.Laboratorio di Citogenetica Medica e Genetica MolecolareCentro di Ricerche e Tecnologie Biomediche IRCCS-Istituto Auxologico ItalianoMilanItaly

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