Copyright@ Katiane Sayão Souza Cabral | Biomed J Sci & Tech Res | BJSTR. MS.ID.006443. 32207 Case Report ISSN: 2574 -1241 DOI: 10.26717/BJSTR.2021.40.006443 Pontocerebellar Hypoplasia Caused by De Novo Mutation in PAFAH1B1 (LIS1) Gene Katiane Sayão Souza Cabral 3 *, Luciana Inuzuka-Nakaharada 3 , Leandro Tavares Lucato 2 and Fernando Kok 1,3 1 Mendelics Genomic Analysis, Brazil 2 Department of Radiology, University of Sao Paulo (USP) School of Medicine, Brazil 3 Department of Neurology, USP School of Medicine, Brazil *Corresponding author: Katiane Sayão Souza Cabral, Department of Neurology, USP School of Medicine, Sao Paulo, Brazil ARTICLE INFO ABSTRACT Received: November 26, 2021 Published: December 06, 2021 Citation: Katiane Sayão Souza Cabral, Luciana Inuzuka-Nakaharada, Leandro Tavares Lucato, Fernando Kok. Pontoc- erebellar Hypoplasia Caused by De novo Mutation in PAFAH1B1 (LIS1) Gene. Bi- omed J Sci & Tech Res 40(3)-2021. BJSTR. MS.ID.006443. Keywords: Pontocerebellar Hypoplasia; PAFAH1B1; LIS1; Whole Exome Sequenc- ing; Brain Malformation Background: Pontocerebellar hypoplasia (PCH) is a genetically heterogeneous condition, characterized by malformation of the cerebellum, the ventral portion of the pons and inferior olivary nucleus, as well as supratentorial atrophic alterations. Cortical migration defects such as lissencephaly may be associated. To date, at least thirteen subtypes of PCH with distinct genotypes and phenotypes have been described. Case Report: We report a case of classical PCH, without cortical migration defect, presented with severe global developmental delay, spasticity and dystonia. Whole exome sequencing detected a missense heterozygous mutation in exon 8 of PAFAH1B1 gene. Parental analysis confirmed that it was a novel de novo mutational event, supporting its association with PCH. Conclusion: Pathogenic variants in PAFAH1B1, which have been widely associated with laminar heterotopia and lissencephaly, had never been linked to isolated PCH. However, we present a case report in which this association was found. Does this case report bring a new phenotype for an “old” gene, or an “old” phenotype with a “new” gene? Abbreviations: PCH: Pontocerebellar Hypoplasia; PAFAH1B1: Platelet-Activating Factor Acetylhydrolase IB Subunit Alpha Gene; LIS1: Lissencephaly 1 Gene; DCX: X-Linked Doublecortin Gene; ARX: Aristaless-Related Homeobox X-Linked Gene; tRNA: Transfer Ribonucleic Acid; TSEN2: tRNA- Splicing Endonuclease Subunit 2; SEPSECS: O-Phosphoserine t-RNA Selenocysteine tRNA Synthase; CLAM: Cerebellar Atrophy With Progressive Microcephaly; RARS2: Arginyl-tRNA Synthetase 2; VRK1: Vaccinia Related Kinase 1; CASK: X-Linked Calcium/Calmodulin-Dependent Serine Protein Kinase; WD40: Water Displacement 40 th Formula Introduction The advance of gene sequencing techniques has made it possible to determine the genetic origin of an increasing number of central nervous system malformations which previously did not have a defined etiology. Pontocerebellar hypoplasia (PCH) is a robust example of great variability of phenotypes associated with a specific group of malformations, characterized by atrophic changes of the cerebellar vermis and hemispheres, the ventral portion of the pons and inferior olivary nucleus, often associated with defects in