Abstract:
Background:
Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations
in
PLA2G6
. The disease commonly affects children below 3 years of age and presents with delay in motor skills,
optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies
from Sub Saharan Africa are almost non-existent.
Case presentation:
Two Sudanese siblings presented, at ages 18 and 24 months, with regression in both motor
milestones and speech development and hyper-reflexia. Brain MRI showed bilateral and symmetrical T2/FLAIR
hyperintense signal changes in periventricular areas and basal ganglia and mild cerebellar atrophy. Whole exome
sequencing with confirmatory Sanger sequencing were perf
ormed for the two patients and healthy family members. A
novel variant (NM_003560.2 c.1427 + 2 T > C) acting on a splic
e donor site and predicted to lead to skipping of exon 10
was found in
PLA2G6
. It was found in a homozygous state in the two patients and homozygous reference or heterozygous
in five healthy family members.
Conclusion:
This variant has one very strong (loss of function mutation) and three supporting evidences for its
pathogenicity (segregation with the disease, multiple computational evidence and specific patients
’
phenotype).
Therefore this variant can be currently annotated as
“
pathogenic
”
. This is the first study to report mutations in
PLA2G6
gene in patients from Sudan
