Recessive mutations in ATP8A2 cause severe hypotonia, cognitive impairment, hyperkinetic movement disorders and progressive optic atrophy

Orphanet Journal of Rare Diseases
Hugh J McMillanGrace Yoon

Abstract

ATP8A2 mutations have recently been described in several patients with severe, early-onset hypotonia and cognitive impairment. The aim of our study was to characterize the clinical phenotype of patients with ATP8A2 mutations. An observational study was conducted at multiple diagnostic centres. Clinical data is presented from 9 unreported and 2 previously reported patients with ATP8A2 mutations. We compare their features with 3 additional patients that have been previously reported in the medical literature. Eleven patients with biallelic ATP8A2 mutations were identified, with a mean age of 9.4 years (range 2.5-28 years). All patients with ATP8A2 mutations (100%) demonstrated developmental delay, severe hypotonia and movement disorders, specifically chorea or choreoathetosis (100%), dystonia (27%) and facial dyskinesia (18%). Optic atrophy was observed in 78% of patients for whom funduscopic examination was performed. Symptom onset in all (100%) was noted before 6 months of age, with 70% having symptoms noted at birth. Feeding difficulties were common (91%) although most patients were able to tolerate pureed or thickened feeds, and 3 patients required gastrostomy tube insertion. MRI of the brain was normal in 50% of the patients...Continue Reading

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Citations

Dec 21, 2018·Omics : a Journal of Integrative Biology·Soujanya D YelamanchiT S Keshava Prasad
Oct 16, 2019·Journal of Neurology·Claire GuissartMichel Koenig
Jun 11, 2020·Current Opinion in Neurology·Dora Steel, Manju A Kurian
Jul 14, 2020·Current Opinion in Neurology·Dora Steel, Manju A Kurian
Aug 11, 2020·Journal of Neural Transmission·José Fidel Baizabal-Carvallo, Francisco Cardoso
Oct 21, 2020·Journal of Clinical Laboratory Analysis·Malihe MohamadianAli Akbar Momen
Feb 16, 2021·Tropical Animal Health and Production·Mohammad AlmasiMohammad Hossein Moradi
Feb 11, 2021·Human Mutation·Erfan HeidariMasoud Garshasbi
Mar 9, 2021·Clinical Genetics·Joana DamásioJorge Sequeiros
May 16, 2021·Proceedings of the National Academy of Sciences of the United States of America·Emilie J RichardsChristopher H Martin

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Methods Mentioned

BETA
exome sequencing
biopsy
PCR
Protein
electrophoresis

Software Mentioned

Samtools
HaplotypeCaller
mem
SnpEff
Mutation Taster
PhyloP
Polyphen
SIFT
Image Studio Lite
MetaSVM

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