Identification of a novel CTCF mutation responsible for syndromic intellectual disability - a case report
Fatma Bastaki1, Pratibha Nair2, Madiha Mohamed1
1Pediatric Department, Latifa Hospital, Dubai Health Authority, Dubai, United Arab Emirates.
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.
Insights
Autosomal dominant mental retardation 21 (MRD21) is a rare genetic disorder caused by mutations in the CTCF gene. This study details a new Emirati patient with a de novo mutation, expanding the understanding of MRD21.
Area of Science:
- Genetics
- Molecular Biology
- Human Disease
Background:
- Autosomal dominant mental retardation 21 (MRD21) is a rare condition characterized by intellectual disability, short stature, microcephaly, and facial dysmorphisms.
- MRD21 is associated with mutations in the CCCTC-binding factor (CTCF) gene, a critical transcriptional regulator involved in chromatin structure.
- Previous cases of MRD21, primarily identified through frameshift mutations, have been limited.
Observation:
- This study reports on an Emirati patient presenting with clinical and molecular characteristics of MRD21.
- A novel de novo frameshift mutation (p.Lys206Profs*13) in the CTCF gene was identified using whole exome sequencing and confirmed via Sanger sequencing.
- In silico analysis suggests this mutation is functionally damaging and may trigger nonsense-mediated mRNA decay.
Findings:
- The identified frameshift mutation in CTCF represents a new molecular cause for MRD21.
- Clinical comparison reveals shared symptoms with previously reported MRD21 cases, alongside some novel observations.
- This case contributes to a more comprehensive definition of MRD21's clinical spectrum and genetic basis.
Implications:
- This research expands the known mutational spectrum of the CTCF gene in relation to MRD21.
- The findings enhance the understanding of the molecular mechanisms underlying intellectual disability and developmental disorders.
- Further research into CTCF function and its role in neurodevelopment is warranted.
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