Review for 10.1186/1471-230X-9-8 (2009)

Reviewer's report
Title:Three novel mutations in the lactase gene (LCT) underlying congenital
lactase deficiency (CLD)
Version: 1Date:18 July 2008
Reviewer: Mauro Congia
Reviewer's report:
The paper reports DNA sequence analyses performed in patients with congenital
lactase deficiency (CLD), a rare disease mostly restricted to the Finnish
population. The authors posed the question if the disease, when present
elsewhere, is associated with the same mutations as those found in Finland.
Indeed, the disease is present also in continental Europe and is associated with
both already reported and with 3 novel mutations.
Patients are clinically well characterized, methods of DNA sequencing and
prediction analysis of mutations by using ClustalW, Blosum62, PolyPhen, SIFT
and Panther PSEC programs are appropriate and well described.
The data sound interesting and may indicate that CLD might be more common
than previously thought also in countries other than Finland.
The manuscript adheres to the relevant standards for reporting and data
deposition and the discussion and conclusions are well balanced and adequately
supported by the data.
Limitations of the work, as for example the small size of the intestinal specimen
of case 2 that did not permit an estimation of exact lactase value, are clearly
stated.
The authors clearly acknowledge relevant previous results, both published and
unpublished.
The title and abstract report accurately what has been found and the
conclusions.
The writing is acceptable.
Minor Essential Revisions:
a) Why some patients were discharged on a soy protein-based formula? Also,
the case 1 patient who remained well on a lactose-free cow’s milk protein-based
formula under 3 months of age was discharged on a lactose-free soy
protein-based formula, whilst the case 2 patient took a lactose-free whey-based,
hydrolyzed formula for all the first year of life.
It is not clear to me, but perhaps clinicians felt it was more prudent to keep the
patients not only on a lactose-free diet but also without a possible confounding
effect of milk proteins because of a temporary cow's milk protein intolerance. If
this is the reason it should be clearly underscored in the section “case
description”.
b) Figure 1 could be eliminated (it does not increase the clarity as mutations are
already well reported in table 1, figure 2 and figure 3) and substituted with a table
reporting the positions and sequences of the primers used to amplify LPH for the
sequence analysis (instead of providing the sequences only upon request).
c) on page 12 in the Discussion section is a spelling mistake (“chance” instead of
“change”).
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I do not have you in the past five years received reimbursements, fees, funding,
or salary from an organisation that may in any way gain or lose financially from
the publication of this paper, either now or in the future.
I do not hold any stocks or shares in an organisation that may in any way gain or
lose financially from the publication of this paper, either now or in the future.
I do not hold or are not currently applying for any patents relating to the content
of the manuscript. I do not have received reimbursements, fees, funding, or
salary from an organization that holds or has applied for patents relating to the
content of the manuscript.
I do not have any other financial competing interests.
I do not have any non-financial competing interests in relation to this paper.