A novel mutation in the proteolytic domain of LONP1 causes atypical CODAS syndrome.
Cerebral, ocular, dental, auricular, skeletal (CODAS) syndrome is a rare autosomal recessive multisystem disorder caused by mutations in LONP1. It is characterized by intellectual disability, cataracts, delayed tooth eruption, malformed auricles and skeletal abnormalities. We performed whole-exome sequencing on a 12-year-old Japanese male with severe intellectual disability, congenital bilateral cataracts, spasticity, hypotonia with motor regression and progressive cerebellar atrophy with hyperintensity of the cerebellar cortex on T2-weighted images. We detected compound heterozygous mutation in LONP1. One allele contained a paternally inherited frameshift mutation (p.Ser100Glnfs*46). The other allele contained a maternally inherited missense mutation (p.Arg786Trp), which was predicted to be pathogenic by web-based prediction tools. The two mutations were not found in Exome Variant Server or our 575 in-house control exomes. Some features were not consistent with CODAS syndrome but overlapped with Marinesco-Sjögren syndrome, a multisystem disorder caused by a mutation in SIL1. An atypical mutation site may result in atypical presentation of the LONP1 mutation.
Department of Pediatric Neurology, Miyagi Children's Hospital, Miyagi, Japan.
Takehiko
T
Inui
Department of Pediatric Neurology, Miyagi Children's Hospital, Miyagi, Japan.
Mai
M
Anzai
Department of Pediatric Neurology, Miyagi Children's Hospital, Miyagi, Japan.|Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
Yusuke
Y
Takezawa
Department of Pediatric Neurology, Miyagi Children's Hospital, Miyagi, Japan.
Wakaba
W
Endo
Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
Yosuke
Y
Kakisaka
Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
Atsuo
A
Kikuchi
Department of Pediatrics, Ekoh-Ryoikuen, Sendai, Japan.
Akira
A
Onuma
Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
Shigeo
S
Kure
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Ichizo
I
Nishino
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Chihiro
C
Ohba
Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Hirotomo
H
Saitsu
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Naomichi
N
Matsumoto
Department of Pediatric Neurology, Miyagi Children's Hospital, Miyagi, Japan.|Department of Pediatrics, Tohoku University School of Medicine, Sendai, Japan.
Kazuhiro
K
Haginoya
D049069:ATP-Dependent Proteases / Q000235:genetics*; D002648:Child; D019465:Craniofacial Abnormalities / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005124:Eye Abnormalities / Q000235:genetics* / Q000503:physiopathology; D016368:Frameshift Mutation / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000235:genetics* / Q000503:physiopathology; D006618:Hip Dislocation, Congenital / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000503:physiopathology; D000072417:Protein Domains / Q000235:genetics; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000503:physiopathology; D014071:Tooth Abnormalities / Q000235:genetics* / Q000503:physiopathology
D024101:Mitochondrial Proteins; D049069:ATP-Dependent Proteases; C000595973:LONP1 protein, human