Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family.
BMC Med Genet. 2018-05-08; 19(1):
DOI: 10.1186/s12881-018-0592-y
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1. BMC Med Genet. 2018 May 8;19(1):72. doi: 10.1186/s12881-018-0592-y.
Case report of a novel homozygous splice site mutation in PLA2G6 gene causing
infantile neuroaxonal dystrophy in a Sudanese family.
Elsayed LEO(1), Mohammed IN(2), Hamed AAA(2), Elseed MA(2), Salih MAM(3), Yahia
A(2)(4), Siddig RA(2), Amin M(2), Koko M(5)(6), Elbashir MI(2), Ibrahim ME(5),
Brice A(7)(8), Ahmed AE(9), Stevanin G(7)(10)(8).
Author information:
(1)Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum,
Sudan. .
(2)Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum,
Sudan.
(3)Division of Pediatric Neurology, Department of Pediatrics, College of
Medicine, King Saud University, Riyadh, Saudi Arabia.
(4)Department of Biochemistry, Faculty of Medicine, National University,
Khartoum, Sudan.
(5)Department of Molecular Biology, Institute of Endemic Diseases, University of
Khartoum, Khartoum, Sudan.
(6)Department of Neurology and Epileptology, Hertie Institute for Clinical Brain
Research, Tuebingen, Germany.
(7)Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR7225,
Sorbonne Universités, UPMC Université Paris VI UMR_S1127, 75013, Paris, France.
(8)Department of genetics, APHP Pitié-Salpêtrière Hospital, 75013, Paris, France.
(9)Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum,
Sudan. .
(10)Ecole Pratique des Hautes Etudes, EPHE, PSL research university, 75014,
Paris, France.
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
performed for the two patients and healthy family members. A novel variant
(NM_003560.2 c.1427 + 2 T > C) acting on a splice 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.
DOI: 10.1186/s12881-018-0592-y
PMCID: PMC5941609
PMID: 29739362 [Indexed for MEDLINE]