Alaa Eskandrani1, Amal AlHashem2, El-Sayed Ali3, Saad AlShahwan1, Kalthoum Tlili4, Khaled Hundallah1, Brahim Tabarki5. 1. Division of Pediatric Neurology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. 2. Division of Pediatric Genetics, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. 3. Department of Pediatrics, King Fahad Military Medical Complex, Dhahran, Saudi Arabia. 4. Division of Neuroradiology, Department of Radiology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. 5. Division of Pediatric Neurology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia. Electronic address: btabarki@hotmail.com.
Abstract
BACKGROUND: Mutations in AFG3L2, a gene encoding a subunit of the mitochondrion m-AAA protease, cause spinocerebellar ataxia type 28 and recessive spastic ataxia type 5. Neuroimaging shows cerebellar atrophy. METHODS: Retrospective review of the patient charts including their clinical evaluation and molecular genetic, neurodiagnostic, and neuroradiological investigations. RESULTS: We describe five members of a large consanguineous family with a severe mitochondrial disease phenotype in the form of regression of the developmental milestones in the first year of life, refractory epilepsy, progressive microcephaly, increased blood lactate, basal ganglia involvement, and premature death. Exome sequencing showed homozygous mutation of the AFG3L2 gene in all individuals: c.1714G>A (p.Ala572Thr). CONCLUSIONS: Our findings add to the phenotypic, neuroradiological, genetic, and biochemical spectrum of AFG3L2 mutations.
BACKGROUND: Mutations in AFG3L2, a gene encoding a subunit of the mitochondrion m-AAA protease, cause spinocerebellar ataxia type 28 and recessive spastic ataxia type 5. Neuroimaging shows cerebellar atrophy. METHODS: Retrospective review of the patient charts including their clinical evaluation and molecular genetic, neurodiagnostic, and neuroradiological investigations. RESULTS: We describe five members of a large consanguineous family with a severe mitochondrial disease phenotype in the form of regression of the developmental milestones in the first year of life, refractory epilepsy, progressive microcephaly, increased blood lactate, basal ganglia involvement, and premature death. Exome sequencing showed homozygous mutation of the AFG3L2 gene in all individuals: c.1714G>A (p.Ala572Thr). CONCLUSIONS: Our findings add to the phenotypic, neuroradiological, genetic, and biochemical spectrum of AFG3L2 mutations.
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