A novel SYNJ1 homozygous variant causing developmental and epileptic encephalopathy in an Afro‐Caribbean individual. Issue 1 (23rd September 2022)

• Record Type: Journal Article
• Authors: Maj, Mary; Taylor, Christie L.; Landau, Kevin; Toriello, Helga V.; Li, Dong; Bhoj, Elizabeth J.; Hakonarson, Hakon; Nelson, Beverly; Gluschitz, Sarah; Walker, Ruth H.; Sobering, Andrew K.
• Is Part Of: Molecular genetics & genomic medicine. Volume 11:Issue 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-23
• Subjects: developmental and epileptic encephalopathy -- synaptojanin 1 -- SYNJ1; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.2064
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: SYNJ1 encodes Synaptojanin‐1, a dual‐function poly‐phosphoinositide phosphatase that is expressed in the brain to regulate neuronal synaptic vesicle dynamics. Biallelic SYNJ1 variants cause a spectrum of clinical manifestations, from early onset parkinsonism to developmental and epileptic encephalopathy. Methods: Proband‐only exome sequencing was used to identify a homozygous SYNJ1 pathogenic variant in an individual with epileptic encephalopathy. Sanger sequencing was used to confirm the variant. Results: We present an Afro‐Caribbean female who developed uncontrollable seizures shortly after birth, accompanied by developmental delay and severe generalized dystonia. She had homozygosity for a novel c.242‐2A > G variant in SYNJ1 with both parents being heterozygous carriers. An older sister was reported to have had a similar presentation but was not examined. Both siblings died at an approximate age of 16 years. Conclusions: We report a novel pathogenic variant in SYNJ1 present in homozygosity leading to developmental and epileptic encephalopathy. Currently, there are only 4 reports describing 10 individuals with SYNJ1‐ related developmental and epileptic encephalopathy. This case expands the clinical knowledge and the allelic heterogeneity associated with SYNJ1 variants. Abstract : We present an individual with developmental and epileptic encephalopathy due to homozygosity for a novel SYNJ1 pathogenic c.242‐2A>G variant. The SYNJ1 protein functions to regulate synaptic vesicle recycling in neurons. Very few papers describing SYNJ1 variants are in the medical literature.