title: A newly recognized autosomal recessive syndrome affecting neurologic function and vision.
abstract: Genetic factors represent an important etiologic group in the causation of intellectual disability. We describe a Saudi Arabian family with closley related parents in which four of six children were affected by a congenital cognitive disturbance. The four individuals (aged 18, 16, 13, and 2 years when last examined) had motor and cognitive delay with seizures in early childhood, and three of the four (sparing only the youngest child) had progressive, severe cognitive decline with spasticity. Two affected children had ocular malformations, and the three older children had progressive visual loss. The youngest had normal globes with good functional vision when last examined but exhibited the oculodigital sign, which may signify a subclinical visual deficit. A potentially deleterious nucleotide change (c.1A>G; p.Met1Val) in the C12orf57 gene was homozygous in all affected individuals, heterozygous in the parents, and absent in an unaffected sibling and >350 normal individuals. This gene has no known function. This family manifests a autosomal recessive syndrome with some phenotypic variability that includes abnormal development of brain and eyes, delayed cognitive and motor milestones, seizures, and a severe cognitive and visual decline that is associated with a homozygous variant in a newly identified gene.
authors: Division of Pediatric Neurology, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors: Mustafa A
authors: MA
authors: Salih
authors: Andreas
authors: A
authors: Tzschach
authors: Darren T
authors: DT
authors: Oystreck
authors: Hamdy H
authors: HH
authors: Hassan
authors: Abdulmajeed
authors: A
authors: AlDrees
authors: Salah A
authors: SA
authors: Elmalik
authors: Heba Y
authors: HY
authors: El Khashab
authors: Thomas F
authors: TF
authors: Wienker
authors: Khaled K
authors: KK
authors: Abu-Amero
authors: Thomas M
authors: TM
authors: Bosley
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000000981:diagnostic imaging / Q000235:genetics*; D002874:Chromosome Mapping; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D020271:Heredodegenerative Disorders, Nervous System / Q000000981:diagnostic imaging / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D011859:Radiography; D012529:Saudi Arabia; D017422:Sequence Analysis, DNA; D035781:Siblings; D014786:Vision Disorders / Q000235:genetics*