Open AccessHomozygous Missense Variation in <b><i>PNPLA8</i></b> Causes Prenatal-Onset Severe Neurodegeneration
Author(s) -
Suzena Masih,
Amita Moirangthem,
Shubha R. Phadke
Publication year - 2021
Publication title -
molecular syndromology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.609
H-Index - 36
eISSN - 1661-8777
pISSN - 1661-8769
DOI - 10.1159/000513524
Subject(s) - missense mutation , neurodegeneration , biology , lactic acidosis , genetics , medicine , endocrinology , bioinformatics , mutation , disease , gene
The patatin-like protein family plays an important role in various biological functions including lipid homeostasis, cellular growth, and signaling. Conserved across species, the patatin domain is shared by all 9 members of the PNPLA family without redundancy in the coding sequences. The defective function of PNPLA2 , PNPLA6 , and PNPLA9 are known to cause mitochondrial-related neurodegeneration. Recently, PNPLA8 has been associated with mitochondrial myopathy and poor weight gain with lactic acidosis in 3 unrelated families. Using whole-exome sequencing, we identified a homozygous novel missense variation c.1874A>G in the patatin domain of PNPLA8 . The patient had prenatal-onset severe and progressive neurodegeneration with mortality in infancy.