Peer Review History

Original SubmissionJuly 12, 2019
Decision Letter - Emanuele Buratti, Editor

[EXSCINDED]

Two novel and correlated CF-causing insertions in the (TG)mTn tract of the CFTR gene

PONE-D-19-19571

Dear Dr. Lucarelli,

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PLOS ONE

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Reviewers' comments:

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Comments to the Author

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Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: N/A

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: The manuscript is very clear and reported two novel and related pathogenic variants of the Cystic Fibrosis ransmembrane conductance Regulator (CFTR) gene. Two patients in the same region (South of Marche Region, Central Italy) have alterations that have not been previously described in literature. Both patients with diagnosis of Cystic Fibrosis (CF) are heterozygous p.Phe508del, and in trans the insertion of part of intron 10 in intron 9 of the CFTR gene, within the (TG)m repeat. The molecular lesions resulted to be very similar in both patients, with only a difference in the number of T in the poly-T stretch. After characterization at RNA level, a complete anomalous splicing, without exon 10, from the allele with the insertion of both patients has been shown. Consequently, these alleles with the insertions are expected to contribute to the formation of a non functional CFTR protein.

All figures and their legends are clear and well documented.

For statistical tests, expression data were evaluated using analysis of variance (ANOVA) by GraphPad Prism 5.

A p<0.05 was considered statistically significant. So it's the reason why I think that the statistical analysis been performed appropriately and rigorously.

Reviewer #2: Cystic fibrosis is an important and common genetic disorder especially among Caucasians, and regarding the complexity of phenotypes encountered in patients and cases which remain genetically undiagnosed, it is therefore important to present new mutations which complete our knowledge about the molecular mechanisms of disease occurence and genotype- phenotype correlation.

In the present manuscript, authors presented a new mutation resulting from internal insertion within intron 9 near the TG tract, affecting the processing of RNA. The mutation analysis was well conducted both structurally (at the level of DNA) and functionnally (at the level of cDNA). All sections of the manuscript are well presented.

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Reviewer #1: No

Reviewer #2: Yes: Haleh Akhavan-Niaki

Formally Accepted
Acceptance Letter - Emanuele Buratti, Editor

PONE-D-19-19571

Two novel and correlated CF-causing insertions in the (TG)mTn tract of the CFTR gene

Dear Dr. Lucarelli:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

For any other questions or concerns, please email plosone@plos.org.

Thank you for submitting your work to PLOS ONE.

With kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Emanuele Buratti

Academic Editor

PLOS ONE

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