Identification of a New Mutation in RSK2, the Gene for Coffin–Lowry Syndrome (CLS), in Two Related Patients with Mild and Atypical Phenotypes

Round 1

Reviewer 1 Report

The manuscript is written well enough.

However, the message is not novel. CLS may present as a clinical spectrum, and this missense mutation results in a variable manner in the described family. The functional studies are convincing that the mutation (s) alter kinase activity.

The English needs revision by someone whose first language is English. There are a number of grammatical / tense issues which need to be addresses. For example, gait is spelt as gate in 2 of 3 instances. A number of the sentences are too long and thus a bit confusing.

"Mental retardation"  is no longer used, and cognitive issues should be referred to as "intellectual disability". The terminology is used inconsistently within the manuscript.

Care also needs to be taken with abbreviations. Also used inconsistently throughout. When describing measurements, the cm should come after the number , e.g. 162 cm rather than cm 163

The paper twice refers to the "health status' of the proband's mother, but there is no detail in the manuscript. 

Author Response

Please see the attachment

Author Response File: Author Response.docx

Reviewer 2 Report

The authors report on a nephew/uncle pair with intellectual disability (ID) and dysmorphic features. They detected a novel missense variant in the X-chromosomal gene RSK2 in both patients and in the mother of the proband. Mutations in RSK2 are associated with Coffin-Lowry syndrome, and the clinical features of the patients are compatible with this disorder. Functional analyses demonstrated reduced kinase activity for this variant and for another missense variant involving the same amino acid residue.

 

Comments:

The term “mental retardation” should be avoided (use instead intellectual disability).

The term “mutation” needs to be replaced by “variant”.

The manuscript needs some language editing. Examples:

“gate” (sic), instead of gait

“highlight: stature” (sic) for height

“lower lip no thick” (sic)

Author Response

Please see the attachment

Author Response File: Author Response.docx