ClinVar

In 2 Scottish sisters and an unrelated English patient, all with Coats plus syndrome (CRMCC1; 612199), Anderson et al. (2012) identified compound heterozygosity for 2 mutations in the CTC1 gene: a 4-bp deletion (724_727delAAAG) in exon 5, resulting in a frameshift and premature termination, and a 2959C-T transition in exon 18, resulting in an arg987-to-trp (R987W; 613129.0002) substitution. The missense mutation affected a residue well-conserved among mammals, and neither mutation was found in 1,730 controls. The patients had previously been reported by Briggs et al. (2008). All had intrauterine growth retardation, intracranial calcifications, leukoencephalopathy, early-onset retinal changes, and gastrointestinal ectasia. The sisters both had gray hair, translucent skin, and dystrophic nails, and the English patient had anemia. One of the sisters and the English patient had early-onset bone fractures. The 2 sisters died in their early twenties of gastrointestinal bleeding. One of the patients was found to have shortened telomere lengths in white blood cells, and each heterozygous parent had telomere lengths at the lower range of normal.

Keller et al. (2012) reported an 18-year-old girl who was compound heterozygous for 724_727delAAAG and a 3-bp deletion (c.2954_2956delGTT; 613129.0012) in the CTC1 gene. The patient presented at age 15 years with classic features of dyskeratosis congenita (see, e.g., 127550), including bone marrow failure, abnormalities in skin pigmentation, nail dysplasia, and graying hair. She also had short stature, osteopenia, decreased pulmonary function, and blurry vision associated with sheathed vessels and microaneurysm formation in the retina. Brain MRI showed calcifications in the right thalamus, and telomeres were shortened significantly. Neurologic function was normal. Patient fibroblasts showed a defect in outgrowth as well as rapid senescence compared to controls. Keller et al. (2012) noted that both CTC1 mutations had been reported in patients with Coats plus syndrome, suggesting that Coats plus syndrome and DKC show phenotypic and genetic overlap, consistent with a telomere-related disease.