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A neurodegenerative mitochondrial disease phenotype due to biallelic loss‐of‐function variants in PNPLA8 encoding calcium‐independent phospholipase A2γ
Author(s) -
Shukla Anju,
Saneto Russell P.,
Hebbar Malavika,
Mirzaa Ghayda,
Girisha Katta M.
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38687
Subject(s) - neurodegeneration , biology , microcephaly , phenotype , lactic acidosis , loss function , exome sequencing , atrophy , mitochondrion , neuroscience , genetics , disease , endocrinology , medicine , gene
Animal studies have demonstrated the critical roles of the patatin‐like protein family plays in cellular growth, lipid homeostasis, and second messenger signaling the nervous system. Of the nine known calcium‐independent phospholipase A2γ, only PNPLA2 , PNLPA6 , PNPLA9 and most recently a single patient with PNPLA8 are associated with mitochondrial‐related neurodegeneration. Using whole exome sequencing, we report two unrelated individuals with variable but similar clinical features of microcephaly, severe global developmental delay, spasticity, lactic acidosis, and progressive cerebellar atrophy with biallelic loss‐of‐function variants in PNPLA8 .