Executive and Attentional Disorders, Epilepsy and Porencephalic Cyst in Autosomal Recessive Cerebellar Ataxia Type 3 Due to <b><i>ANO10</i></b> Mutation

Abstract

Background:ANO10 mutations have recently been reported in autosomal recessive cerebellar ataxia type 3 (ARCA3). The objective of this study was to describe the phenotype of 2 siblings with compound heterozygous ANO10 mutations and progressive cerebellar ataxia, epilepsy, and cognitive impairment. A porencephalic cyst was also described in one of them and a coenzyme Q10 deficiency in the other one. Methods: We performed neurological, neuropsychological, electromyographic, electroencephalic and MRI examinations in 2 siblings with compound heterozygous ANO10 mutations. Results: We reported for the first time the neuropsychological profile of 2 ARCA3 patients showing an adult-onset executive and attentional syndrome. Both presented epilepsy. One of them presented a porencephalic cyst. Conclusion: These results suggest that executive and attentional disorders are impaired in ANO10 mutation. In addition, epilepsy and porencephalic cysts were also described in our ARCA3 patients, the cyst thus expanding the clinical phenotype of ARCA3 patients due to ANO10 mutation.

The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K

“…This hypothesis provides a new direction for research into the underlying biology of these ataxias and the development of novel therapies. 15…”

The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K

“…TMEM16K is a widely distributed 11 , but relatively unstudied member of the TMEM16 family. Truncations and missense variants of TMEM16K (ANO10) are associated with the autosomal recessive spinocerebellar ataxia SCAR10 12,13 (as known as ARCA3 14–16 or ATX-ANO10 17 ). SCAR10 causes cerebellar ataxia, with cerebellar atrophy evident in magnetic resonance imaging scans of brains and coenzyme Q10 deficiency found in muscle biopsy, fibroblasts and cerebrospinal fluid 12,13,18,19 .…”

Secondary CoQ10 deficiency, bioenergetics unbalance in disease and aging

“…Several cases of CoQ 10 deficiency are associated with mutations in channels or carriers located at the plasma membrane. Mutations in the ANO10 gene, coding for a member of the anoctamin family of transmembrane proteins with calcium‐activated chloride channel activities, produce spinocerebellar ataxia associated with CoQ 10 deficiency in skeletal muscle, plasma, and cerebrospinal fluid 128–130 . Another channelopathy with mutations in the SCN2A ‐encoded voltage‐gated sodium channel (Nav1.1) presented CoQ 10 deficiency in muscle, suggesting that CoQ 10 might have a role in calcium signaling 40 .…”