Mutations in the mitochondrial gene C12ORF65 lead to syndromic autosomal recessive intellectual disability and show genotype phenotype correlation.
Homozygosity mapping and exome sequencing in two affected siblings of a consanguineous family with mild intellectual disability, spastic paraplegia, and strabismus revealed a homozygous premature stop mutation at codon 139 of C12ORF65. Two previous studies reported truncating mutations at positions 84 and 132 of the protein. However, symptoms of the referred patients were only partially overlapping. Considering our findings, we now conclude that truncating mutations in C12ORF65 lead to a variable phenotype with intellectual disability, spastic paraplegia, and ophthalmoplegia as common symptoms. Further, we confirm a genotype-phenotype correlation between increasing length of the truncated protein and decreasing severity of symptoms.
Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Schwabachanlage 10, 91054 Erlangen, Germany.
Rebecca
R
Buchert
Steffen
S
Uebe
Farah
F
Radwan
Hasan
H
Tawamie
Shaher
S
Issa
Haruo
H
Shimazaki
Marco
M
Henneke
Arif B
AB
Ekici
André
A
Reis
Rami
R
Abou Jamra
D000328:Adult; D018389:Codon, Nonsense; D005260:Female; D005808:Genes, Recessive; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D024101:Mitochondrial Proteins; D010264:Paraplegia / Q000175:diagnosis / Q000235:genetics; D010375:Pedigree; D010454:Peptide Termination Factors / Q000235:genetics*; D010641:Phenotype; D013285:Strabismus / Q000175:diagnosis / Q000235:genetics; D013577:Syndrome
D018389:Codon, Nonsense; D024101:Mitochondrial Proteins; D010454:Peptide Termination Factors; C551030:MTRFR protein, human
ARID; Homozygosity mapping; NGS; SPG; Syria