TY - JOUR
T1 - Expanding the phenotype of IBA57 mutations
T2 - related leukodystrophy can remain asymptomatic
AU - Hamanaka, Kohei
AU - Miyatake, Satoko
AU - Zerem, Ayelet
AU - Lev, Dorit
AU - Blumkin, Luba
AU - Yokochi, Kenji
AU - Fujita, Atsushi
AU - Imagawa, Eri
AU - Iwama, Kazuhiro
AU - Nakashima, Mitsuko
AU - Mitsuhashi, Satomi
AU - Mizuguchi, Takeshi
AU - Takata, Atsushi
AU - Miyake, Noriko
AU - Saitsu, Hirotomo
AU - van der Knaap, Marjo S.
AU - Lerman-Sagie, Tally
AU - Matsumoto, Naomichi
N1 - Publisher Copyright:
© 2018, The Author(s) under exclusive licence to The Japan Society of Human Genetics.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Biallelic mutations in IBA57 cause a mitochondrial disorder with a broad phenotypic spectrum that ranges from severe intellectual disability to adolescent-onset spastic paraplegia. Only 21 IBA57 mutations have been reported, therefore the phenotypic spectrum of IBA57-related mitochondrial disease has not yet been fully elucidated. In this study, we performed whole-exome sequencing on a Sepharadi Jewish and Japanese family with leukodystrophy. We identified four novel biallelic variants in IBA57 in the two families: one frameshift insertion and three missense variants. The three missense variants were predicted to be disease-causing by multiple in silico tools. The 29-year-old Sepharadi Jewish male had infantile-onset optic atrophy with clinically asymptomatic leukodystrophy involving periventricular white matter. The 19-year-old younger brother, with the same compound heterozygous IBA57 variants, had a similar clinical course until 7 years of age. However, he then developed a rapidly progressive spastic paraparesis following a febrile illness. A 7-year-old Japanese girl had developmental regression, spastic quadriplegia, and abnormal periventricular white matter signal on brain magnetic resonance imaging performed at 8 months of age. She had febrile convulsions at the age of 18 months and later developed epilepsy. In summary, we have identified four novel IBA57 mutations in two unrelated families. Consequently, we describe a patient with infantile-onset optic atrophy and asymptomatic white matter involvement, thus broadening the phenotypic spectrum of biallelic IBA57 mutations.
AB - Biallelic mutations in IBA57 cause a mitochondrial disorder with a broad phenotypic spectrum that ranges from severe intellectual disability to adolescent-onset spastic paraplegia. Only 21 IBA57 mutations have been reported, therefore the phenotypic spectrum of IBA57-related mitochondrial disease has not yet been fully elucidated. In this study, we performed whole-exome sequencing on a Sepharadi Jewish and Japanese family with leukodystrophy. We identified four novel biallelic variants in IBA57 in the two families: one frameshift insertion and three missense variants. The three missense variants were predicted to be disease-causing by multiple in silico tools. The 29-year-old Sepharadi Jewish male had infantile-onset optic atrophy with clinically asymptomatic leukodystrophy involving periventricular white matter. The 19-year-old younger brother, with the same compound heterozygous IBA57 variants, had a similar clinical course until 7 years of age. However, he then developed a rapidly progressive spastic paraparesis following a febrile illness. A 7-year-old Japanese girl had developmental regression, spastic quadriplegia, and abnormal periventricular white matter signal on brain magnetic resonance imaging performed at 8 months of age. She had febrile convulsions at the age of 18 months and later developed epilepsy. In summary, we have identified four novel IBA57 mutations in two unrelated families. Consequently, we describe a patient with infantile-onset optic atrophy and asymptomatic white matter involvement, thus broadening the phenotypic spectrum of biallelic IBA57 mutations.
UR - http://www.scopus.com/inward/record.url?scp=85053854821&partnerID=8YFLogxK
U2 - 10.1038/s10038-018-0516-x
DO - 10.1038/s10038-018-0516-x
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C2 - 30258207
AN - SCOPUS:85053854821
SN - 1434-5161
VL - 63
SP - 1223
EP - 1229
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 12
ER -