PMC4830701_01
(a) Dry skin with ichthyosis in the younger sibling at the age of 3 years. (b) Dry skin with nummular eczema in the elder sibling at the age of 8 years. (c) Sanger confirmation of the mutation. Both affected siblings are homozygous and both parents are heterozygous carriers for R344Q mutation. (d) The conservation of the homozygous missense mutation within the vertebrates (http://www.ebi.ac.uk/Tools/msa/clustalw2/).
BMRI2016-3128735.001.jpg
PMC4830701_01_BMRI2016-3128735.001.jpg
fig1
Physical examination revealed hypoactive deep tendon reflexes, proximal muscle weakness, contractures in the knee of elder sibling, diffuse mild generalized muscle atrophy, dry skin with ichthyosis and multiple nummular eczema in the younger and elder siblings, respectively (Figures 1(a) and 1(b)). The Cologne Center for Genomics VARBANK pipeline v.2.12 (https://varbank.ccg.uni-koeln.de/) used for data analysis for rare autosomal recessive disease in a consanguineous family revealed an unpublished novel homozygous missense variant in the Choline Kinase-Beta (CHKB) gene c.1031G>A in exon 9 causing p.R344Q according to NM_005198.4 (Figure 1(c)). Aggregation Consortium (http://exac.broadinstitute.org/). Arginine at 344 is highly conserved on vertebrates (Figure 1(d)) and analysis of this variant predicted it to be disease causing by MutationTaster (http://www.mutationtaster.org). The R344Q variant was confirmed by Sanger sequencing, which also revealed the homozygosity for the other affected sibling and carrier heterozygosity for the parents (Figure 1(c)).