A novel HCFC1 variant in male siblings with intellectual disability and microcephaly in the absence of cobalamin disorder

Koufaris,Costas; Alexandrou,Angelos; Tanteles,George  A.; Anastasiadou,Violetta; Sismani,Carolina

doi:10.3892/br.2015.559

A novel HCFC1 variant in male siblings with intellectual disability and microcephaly in the absence of cobalamin disorder

Authors:
- Costas Koufaris
- Angelos Alexandrou
- George A. Tanteles
- Violetta Anastasiadou
- Carolina Sismani
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Affiliations: Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, 1683 Nicosia, Cyprus, Department of Clinical Genetics, The Cyprus Institute of Neurology and Genetics, 1683 Nicosia, Cyprus
Published online on: December 18, 2015 https://doi.org/10.3892/br.2015.559
Pages: 215-218

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Abstract

Approximately 10-15% of intellectual disability (ID) cases are caused by genetic aberrations affecting chromosome X, a condition termed X‑linked ID (XLID). Examination by whole-exome sequencing of two male siblings with microcephaly and suspected XLID with an unknown genetic basis revealed that they were both hemizygous for a predicted pathogenic variant (p.Ala897Val) causing a non‑synonymous substitution of an evolutionary conserved amino acid within the host cell factor C1 (HCFC1) gene. Subsequent analysis determined that this was a rare variant not identified in 100 control individuals or in online databases of control individuals. Recent studies have reported mutations affecting HCFC1 in patients with ID and dysmorphic features that are associated with defective cobalamin metabolism. Biochemical investigations did not find evidence of an association between the variant identified in the present study and cobalamin metabolic disorder. This study offers further support for mutations of HCFC1 being implicated in XLID and microcephaly, but that these are not necessarily associated with cobalamin disorder.

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