title: Recessive optic atrophy, sensorimotor neuropathy and cataract associated with novel compound heterozygous mutations in OPA1.
abstract: Mutations in the optic atrophy 1 gene (OPA1) are associated with autosomal dominant optic atrophy and 20% of patients demonstrate extra-ocular manifestations. In addition to these autosomal dominant cases, only a few syndromic cases have been reported thus far with compound heterozygous OPA1 mutations, suggestive of either recessive or semi‑dominant patterns of inheritance. The majority of these patients were diagnosed with Behr syndrome, characterized by optic atrophy, ataxia and peripheral neuropathy. The present study describes a 10-year-old boy with Behr syndrome presenting with early‑onset severe optic atrophy, sensorimotor neuropathy, ataxia and congenital cataracts. He had optic atrophy and was declared legally blind at six years old. Electrophysiological, radiological, and histopathological findings were compatible with axonal sensorimotor polyneuropathy. At birth, he presented with a congenital cataract, which has not been previously described in patients with OPA1 mutations. Whole exome sequencing indicated a pair of novel compound heterozygous mutations: p.L620fs*13 (c.1857‑1858delinsT) and p.R905Q (c.G2714A). Neither mutation was observed in controls (n=300), and thus, they were predicted to be pathogenic by multiple in silico analyses. The mutation sites were highly conserved throughout different vertebrate species. The patients parents did not have any ophthalmic or neurologic symptoms and the results of electrophysiological studies were normal, suggestive of an autosomal recessive pattern of inheritance. The present study identified novel compound heterozygous OPA1 mutations in a patient with recessive optic atrophy, sensorimotor neuropathy and congenital cataracts, indicating an expansion of the clinical spectrum of pathologies associated with OPA1 mutations. Thus, OPA1 gene screening is advisable in the workup of patients with recessive optic atrophy, particularly with Behr syndrome and cataracts.
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135‑710, Republic of Korea.
authors.forename: Jinho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Ewha Womans University School of Medicine, Seoul 120‑750, Republic of Korea.
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Jung
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135‑710, Republic of Korea.
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Hong
authors.affiliation: Department of Radiology, Ewha Womans University School of Medicine, Seoul 120‑750, Republic of Korea.
authors.forename: Jeong Hyun
authors.initials: JH
authors.lastname: Yoo
authors.affiliation: Department of Pathology, Ewha Womans University School of Medicine, Seoul 120‑750, Republic of Korea.
authors.forename: Heasoo
authors.initials: H
authors.lastname: Koo
authors.affiliation: Department of Biological Science, Kongju National University, Konju, Chungnam 314‑701, Republic of Korea.
authors.forename: Ja Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biological Science, Kongju National University, Konju, Chungnam 314‑701, Republic of Korea.
authors.forename: Hyun Dae
authors.initials: HD
authors.lastname: Hong
authors.affiliation: Department of Neurology, Kyung Hee University College of Medicine, Seoul 143‑601, Republic of Korea.
authors.forename: Sang-Beom
authors.initials: SB
authors.lastname: Kim
authors.affiliation: Department of Biological Science, Kongju National University, Konju, Chungnam 314‑701, Republic of Korea.
authors.forename: Ki Wha
authors.initials: KW
authors.lastname: Chung
authors.affiliation: Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135‑710, Republic of Korea.
authors.forename: Byung-Ok
authors.initials: BO
authors.lastname: Choi
mesh_terms: D001259:Ataxia / Q000175:diagnosis / Q000235:genetics*; D001706:Biopsy; D002386:Cataract / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D059472:Exome; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005808:Genes, Recessive; D034381:Hearing Loss / Q000175:diagnosis / Q000235:genetics*; D006579:Heterozygote; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D007866:Leg / Q000000981:diagnostic imaging / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009896:Optic Atrophy / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D029241:Optic Atrophy, Autosomal Dominant / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D013035:Spasm / Q000175:diagnosis / Q000235:genetics*
chemical_list: D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human