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Case Reports
. 2017 Jun 15;18(1):68.
doi: 10.1186/s12881-017-0429-0.

Identification of a novel CTCF mutation responsible for syndromic intellectual disability - a case report

Fatma Bastaki  1 , Pratibha Nair  2 , Madiha Mohamed  1 , Ethar Mustafa Malik  1 , Mustafa Helmi  1 , Mahmoud Taleb Al-Ali  2 , Abdul Rezzak Hamzeh  3
Affiliations
Case Reports

Identification of a novel CTCF mutation responsible for syndromic intellectual disability - a case report

Fatma Bastaki et al. BMC Med Genet. .

Abstract

Background: Autosomal dominant mental retardation 21 (MRD21) is a very rare condition, characterized by short stature, microcephaly, mild facial dysmorphisms and intellectual disability that ranged from mild to severe. MRD21 is caused by mutations in CCCTC-binding factor (CTCF) and this was established through only four unrelated cases, two of which had frameshift mutations. CTCF is a master transcriptional regulator that controls chromatin structure and may serve as insulator and transcriptional activator and repressor.

Case presentation: This study presents, clinically and molecularly, an Emirati patient with de novo frameshift mutation in CTCF. This novel mutation was uncovered using whole exome sequencing and was confirmed by Sanger sequencing in the trio. In silico analysis, using SIFT Indel, indicates that this frameshift; p.Lys206Profs*13 is functionally damaging with the likely involvement of nonsense-mediated mRNA decay.

Conclusions: Upon comparing the clinical picture of the herewith-reported individual with previously reported cases of MRD21, there seems to be many common symptoms, and few new ones that were not observed before. This helps to further define this rare condition and its molecular underpinnings.

Keywords: CCCTC-binding factor; De novo mutation, Arab, case report; Intellectual disability.

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Figures

Fig. 1
Fig. 1
Panel (a) shows the pedigree chart of the patient. Panels (b) and (e) show clinical features of the CTCF mutation in the patient, which include numerous dysmorphisms such as microbrachycephaly, narrow forehead highly arched and bushy eyebrows, deep-seated eyes, broad nasal tip with wide everted nostrils, prominent incisors, and large ears with dysplastic helix and attached ear lobes. Panels (c) and (d) are X-ray radiographs showing the presence of diffuse generalized osteopenia
Fig. 2
Fig. 2
Sequence chromatograms showing the novel CTCF frameshift mutation in a heterozygous state in the patient; Panel (a). Both parents were found to harbor wild type CTCF; Panels (b) and (c), in which the AAAG that is deleted by the mutation is highlighted
See this image and copyright information in PMC

References

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