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2021 Highlights


December 09, 2021

Volume 27, Issue 12

PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans

Intracranial aneurysm (IA) rupture leads to subarachnoid hemorrhage, a sudden-onset disease that often causes death or severe disability. Although genome-wide association studies have identified common genetic variants that increase IA risk moderately, the contribution of variants with large effect remains poorly defined. Using whole-exome sequencing, we identified significant enrichment of rare, deleterious mutations in PPIL4, encoding peptidyl-prolyl cis-trans isomerase-like 4, in both familial and index IA cases. Ppil4 depletion... 


August 01, 2021

Volume 78, Issue 8

DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease

 A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records from US hospitals spanning a range of 1 month to 1.5 years were reviewed for phenotyping. Exomes from a larger validation cohort were analyzed to identify additional rare, large-effect variants in the top candidate gene. Participants included patients with MMD and, when available, their parents. All participants...


March 01, 2021

Volume 175, Issue 3

Exome Sequencing as a Potential Diagnostic Adjunct in Sporadic Congenital Hydrocephalus

Congenital hydrocephalus (CH) affects 1 in 1000 births, is a major cause of morbidity, and costs the US health care system $2 billion annually.1 More than 40% of CH cases are thought to have a genetic etiology. However, only less than 5% of CH cases are associated with a defined gene mutation,1 limiting the utility of genetic testing with targeted approaches and underscoring the need for CH gene discovery. The X-linked recessive form of hydrocephalus associated with...

Koo AB, Elsamadicy AA, Lin IH, et al. Patient Risk Factors Associated With 30- and 90-Day Readmission After Ventriculoperitoneal Shunt Placement for Idiopathic Normal Pressure Hydrocephalus in Elderly Patients: A Nationwide Readmission Study. World Neurosurg. 2021;152:e23-e31. doi:10.1016/j.wneu.2021.04.010
Elsamadicy AA, Koo AB, David WB, et al. Pre-operative headaches and obstructive hydrocephalus predict an extended length of stay following suboccipital decompression for pediatric Chiari I malformation. Childs Nerv Syst. 2021;37(1):91-99. doi:10.1007/s00381-020-04688-2
Elsamadicy AA, Freedman IG, Koo AB, et al. The Effects of Pulmonary Risk Factors on Hospital Resource Use After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis Correction. World Neurosurg. 2021;149:e737-e747. doi:10.1016/j.wneu.2021.01.109
Elsamadicy AA, Koo AB, David WB, et al. Impact of race on outcomes and healthcare utilization following spinal fusion for adolescent idiopathic scoliosis. Clin Neurol Neurosurg. 2021;206:106634. doi:10.1016/j.clineuro.2021.106634
Elsamadicy AA, Freedman IG, Koo AB, et al. Impact of Preoperative Anemia on Outcomes After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis. World Neurosurg. 2021;146:e214-e224. doi:10.1016/j.wneu.2020.10.074
Allington G, Duy PQ, Ryou J, et al. Genomic approaches to improve the clinical diagnosis and management of patients with congenital hydrocephalus [published online ahead of print, 2021 Oct 29]. J Neurosurg Pediatr. 2021;1-10. doi:10.3171/2021.8.PEDS21368
Fomchenko EI, Reeves BC, Sullivan W, et al. Dual activating FGFR1 mutations in pediatric pilomyxoid astrocytoma. Mol Genet Genomic Med. 2021;9(2):e1597. doi:10.1002/mgg3.1597
Barak T, Ristori E, Ercan-Sencicek AG, et al. PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans. Nat Med. 2021;27(12):2165-2175. doi:10.1038/s41591-021-01572-7
Sullivan W, Reeves BC, Duy PQ, et al. Exome Sequencing as a Potential Diagnostic Adjunct in Sporadic Congenital Hydrocephalus. JAMA Pediatr. 2021;175(3):310-313. doi:10.1001/jamapediatrics.2020.4878
Rahmati N, Normoyle KP, Glykys J, et al. Unique Actions of GABA Arising from Cytoplasmic Chloride Microdomains. J Neurosci. 2021;41(23):4957-4975. doi:10.1523/JNEUROSCI.3175-20.2021
Junn A, Dinis J, Kahle KT, Alperovich M. Stepwise Reconstruction of a Large, Self-Inflicted Calvarial Defect [published online ahead of print, 2021 Sep 22]. J Craniofac Surg. 2021;10.1097/SCS.0000000000008192. doi:10.1097/SCS.0000000000008192
Duy PQ, Kahle KT. Intraventricular CSF Turbulence in Pediatric Communicating Hydrocephalus. Neurology. 2021;97(5):246-247. doi:10.1212/WNL.0000000000012237
Elsamadicy AA, Koo AB, David WB, et al. Post-traumatic seizures following pediatric traumatic brain injury. Clin Neurol Neurosurg. 2021;203:106556. doi:10.1016/j.clineuro.2021.106556
DeSpenza T Jr, Carlson M, Panchagnula S, et al. PTEN mutations in autism spectrum disorder and congenital hydrocephalus: developmental pleiotropy and therapeutic targets. Trends Neurosci. 2021;44(12):961-976. doi:10.1016/j.tins.2021.08.007
Kundishora AJ, Singh AK, Allington G, et al. Genomics of human congenital hydrocephalus. Childs Nerv Syst. 2021;37(11):3325-3340. doi:10.1007/s00381-021-05230-8
Diab NS, Barish S, Dong W, et al. Molecular Genetics and Complex Inheritance of Congenital Heart Disease. Genes (Basel). 2021;12(7):1020. Published 2021 Jun 30. doi:10.3390/genes12071020
Robert SM, Reeves BC, Marlier A, Duy PQ, DeSpenza T, Kundishora A, Kiziltug E, Singh A, Allington G, Alper SL, Kahle KT. Inflammatory hydrocephalus. Childs Nerv Syst. 2021 Jun 23. doi: 10.1007/s00381-021-05255-z. Epub ahead of print. PMID: 34164718.
Diab NS, King S, Dong W, Allington G, Sheth A, Peters ST, Kahle KT, Jin SC. Analysis workflow to assess de novo genetic variants from human whole-exome sequencing. STAR Protoc. 2021 Mar 10;2(1):100383. doi: 10.1016/j.xpro.2021.100383. PMID: 33748785; PMCID: PMC7960548.
Kundishora AJ, Peters ST, Pinard A, Duran D, Panchagnula S, Barak T, Miyagishima DF, Dong W, Smith H, Ocken J, Dunbar A, Nelson-Williams C, Haider S, Walker RL, Li B, Zhao H, Thumkeo D, Marlier A, Duy PQ, Diab NS, Reeves BC, Robert SM, Sujijantarat N, Stratman AN, Chen YH, Zhao S, Roszko I, Lu Q, Zhang B, Mane S, Castaldi C, López-Giráldez F, Knight JR, Bamshad MJ, Nickerson DA, Geschwind DH, Chen SL, Storm PB, Diluna ML, Matouk CC, Orbach DB, Alper SL, Smith ER, Lifton RP, Gunel M, Milewicz DM, Jin SC, Kahle KT. DIAPH1 Variants in Non-East Asian Patients With Sporadic Moyamoya Disease. JAMA Neurol. 2021 Jun 14:e211681. doi: 10.1001/jamaneurol.2021.1681. Epub ahead of print. PMID: 34125151; PMCID: PMC8204259.
Omer S, Jin SC, Koumangoye R, Robert SM, Duran D, Nelson-Williams C, Huttner A, DiLuna M, Kahle KT, Delpire E. Protein kinase D1 variant associated with human epilepsy and peripheral nerve hypermyelination. Clin Genet. 2021 Apr 27. doi: 10.1111/cge.13973. Epub ahead of print. PMID: 33904160.
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