Content of review 1, reviewed on January 11, 2020

Khan et al report a family with two affected who were found to have homozygous frameshift mutation in PDCD6IP. Both zebrafish and mouse model showed similar phenotype. Thus, it is likely PDCD6IP is a novel microcephaly-DD/ID gene. I have several easily doable comments:
Kerywords include Saudi Arabia. I do not think it is appropriate to put a country’s name as key word
Microcephaly is considered in less than 2 SD (not 3 SD) or 3 percentile and may cause severe intellectual disability thus I recommend to rephrase the first sentence of introduction.
The second sentence is wrong as well. The authors gave a frequency of 1.3- to 1 in 250,000 and cited two articles. In one of the articles, there is no incidence number (Woods et al) and the second one (Wang et al) provided a number of 1:10,000 and cited another article (for primary microcephaly in consanguineous populations. Considering environmental factors and the most commong genetic syndrome (Down syndrome with a frequency of 1 in 700), the authors number does not make sense.
Can the authors perform Sanger sequencing in the rest of the siblings as much as they can? The segregation within 6 siblings is one of the strongest evidence for the candidacy of the gene. If they performed it, can they show it on the pedigree or write in the text?
At the end of Results section (page 10) The authors state that PDCD6IP is dossage sensitive gene. In the discussion, authors are also stating that it is not clear whether heterozygous deletion cause phenotype (page 11 second paragraph), it is better to delete the paragraph at the end of Results section.
Page 8: Change cognition impairment to cognitive impairment
Table 1: SD for OFC, height and weight,
Table 1: The authors did not use ++, thus they can remove from the legend.
Table 2: The hg19 coordinates the author provide encompases 28 kb region.

Source

    © 2020 the Reviewer.

Content of review 2, reviewed on March 08, 2020

The authors incorporated my recommendations. I do not have any further edits.

Source

    © 2020 the Reviewer.

References

    Amjad, K., Manal, A., Salam, M., Abdulrahman, O., A., K. A., A., W. C., Wafaa, E. 2020. PDCD6IP, encoding a regulator of the ESCRT complex, is mutated in microcephaly. Clinical Genetics.