A Japanese case of cerebellar ataxia, spastic paraparesis and deep sensory impairment associated with a novel homozygous TTC19 mutation.
Misako KuniiHiroshi DoiYuichi HigashiyamaChiharu KugimotoNaohisa UedaJunichi HirataAtsuko Tomita-KatsumotoMari Kashikura-KojimaShun KubotaMidori TaniguchiKei MurayamaMitsuko NakashimaYoshinori TsurusakiNoriko MiyakeHirotomo SaitsuNaomichi MatsumotoFumiaki TanakaPublished in: Journal of human genetics (2015)
Mitochondrial complex III (CIII) deficiency comprises a group of complex and heterogeneous genetic disorders. TTC19 mutations constitute a rare cause of CIII deficiency and are associated with neurological disorders in childhood and adulthood. Herein, we describe a 27-year-old Japanese man with cerebellar ataxia, spastic paraparesis, loss of deep sensation, mild frontal lobe dysfunction and transient psychiatric symptoms. Brain magnetic resonance imaging showed cerebellar atrophy and bilateral high-intensity signals in the inferior olives and regions adjacent to periaqueductal gray matter, on T2-weighted images. On whole-exome sequencing, we detected a novel homozygous frameshift mutation c.157_158dup [p.Pro54Alafs*48] in TTC19. Mitochondrial enzyme assays confirmed mild impairment of CIII enzymatic activity in lymphoblasts, which was consistent with TTC19-related CIII deficiency. His symptoms and radiological findings demonstrated an early stage or mild form of this disease, and further clarify the characteristics of patients with rare TTC19 mutations.
Keyphrases
- high intensity
- early stage
- magnetic resonance imaging
- oxidative stress
- cerebral palsy
- cerebral ischemia
- replacement therapy
- early onset
- mental health
- early life
- botulinum toxin
- computed tomography
- magnetic resonance
- upper limb
- working memory
- depressive symptoms
- high throughput
- sleep quality
- squamous cell carcinoma
- gene expression
- hydrogen peroxide
- lymph node
- physical activity
- smoking cessation
- machine learning
- sentinel lymph node
- subarachnoid hemorrhage
- body composition
- drug induced
- neoadjuvant chemotherapy
- childhood cancer