PMID- 29739362 OWN - NLM STAT- MEDLINE DCOM- 20190225 LR - 20221207 IS - 1471-2350 (Electronic) IS - 1471-2350 (Linking) VI - 19 IP - 1 DP - 2018 May 8 TI - Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family. PG - 72 LID - 10.1186/s12881-018-0592-y [doi] LID - 72 AB - 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. FAU - Elsayed, Liena E O AU - Elsayed LEO AUID- ORCID: 0000-0001-5753-6760 AD - Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum, Sudan. doctorlbo@hotmail.com. FAU - Mohammed, Inaam N AU - Mohammed IN AD - Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum, Sudan. FAU - Hamed, Ahlam A A AU - Hamed AAA AD - Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum, Sudan. FAU - Elseed, Maha A AU - Elseed MA AD - Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum, Sudan. FAU - Salih, Mustafa A M AU - Salih MAM AD - Division of Pediatric Neurology, Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia. FAU - Yahia, Ashraf AU - Yahia A AD - Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum, Sudan. AD - Department of Biochemistry, Faculty of Medicine, National University, Khartoum, Sudan. FAU - Siddig, Rayan A AU - Siddig RA AD - Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum, Sudan. FAU - Amin, Mutaz AU - Amin M AD - Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum, Sudan. FAU - Koko, Mahmoud AU - Koko M AD - Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan. AD - Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, Tuebingen, Germany. FAU - Elbashir, Mustafa I AU - Elbashir MI AD - Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum, Sudan. FAU - Ibrahim, Muntaser E AU - Ibrahim ME AD - Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan. FAU - Brice, Alexis AU - Brice A AD - Institut du Cerveau et de la Moelle epiniere, INSERM U1127, CNRS UMR7225, Sorbonne Universites, UPMC Universite Paris VI UMR_S1127, 75013, Paris, France. AD - Department of genetics, APHP Pitie-Salpetriere Hospital, 75013, Paris, France. FAU - Ahmed, Ammar E AU - Ahmed AE AD - Faculty of Medicine, University of Khartoum, Qasr Street, 11111, Khartoum, Sudan. atahmed10@gmail.com. FAU - Stevanin, Giovanni AU - Stevanin G AD - Institut du Cerveau et de la Moelle epiniere, INSERM U1127, CNRS UMR7225, Sorbonne Universites, UPMC Universite Paris VI UMR_S1127, 75013, Paris, France. AD - Ecole Pratique des Hautes Etudes, EPHE, PSL research university, 75014, Paris, France. AD - Department of genetics, APHP Pitie-Salpetriere Hospital, 75013, Paris, France. LA - eng PT - Case Reports PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180508 PL - England TA - BMC Med Genet JT - BMC medical genetics JID - 100968552 RN - 0 (RNA Splice Sites) RN - EC 3.1.1.4 (Group VI Phospholipases A2) RN - EC 3.1.1.4 (PLA2G6 protein, human) SB - IM MH - Child, Preschool MH - Female MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - Group VI Phospholipases A2/*genetics MH - Homozygote MH - Humans MH - Infant MH - Male MH - *Mutation MH - Neuroaxonal Dystrophies/*genetics MH - *RNA Splice Sites MH - Siblings MH - Sudan MH - Exome Sequencing/*methods PMC - PMC5941609 OTO - NOTNLM OT - Infantile neuroaxonal dystrophy OT - PLA2G6 OT - Sudan OT - Whole exome sequencing COIS- ETHICS APPROVAL AND CONSENT TO PARTICIPATE: This study was approved by the Paris Necker Ethics Committee (France) and the Ethical Committee of the University of Khartoum Medical Campus (Sudan). Written informed consent was obtained from each family member (or parents/legal guardians in case of minors) before participation in the study. CONSENT FOR PUBLICATION: All participants (or parents/legal guardians in case of minors) provided consent for the publication of their clinical details. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER'S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. EDAT- 2018/05/10 06:00 MHDA- 2019/02/26 06:00 PMCR- 2018/05/08 CRDT- 2018/05/10 06:00 PHST- 2017/09/20 00:00 [received] PHST- 2018/04/24 00:00 [accepted] PHST- 2018/05/10 06:00 [entrez] PHST- 2018/05/10 06:00 [pubmed] PHST- 2019/02/26 06:00 [medline] PHST- 2018/05/08 00:00 [pmc-release] AID - 10.1186/s12881-018-0592-y [pii] AID - 592 [pii] AID - 10.1186/s12881-018-0592-y [doi] PST - epublish SO - BMC Med Genet. 2018 May 8;19(1):72. doi: 10.1186/s12881-018-0592-y.