Novel PHOX2B germline mutation in childhood medulloblastoma: a case report

Caiping Ke,Zhuona Chen,Allen Menglin Chen,Bifeng Jiang,Xiaoshun Shi,Jiexia Zhang,Yingjun Luo,Kailing Huang,Huaming Lin,Chaoming Li,Zhouxia Zheng,Yanhui Liu

doi:10.1186/s13053-021-00170-5

Abstract

BackgroundMedulloblastoma is an aggressive brain tumor mostly found in children, few studies on pathogenic germline mutations predisposing this disease was reported.Case presentationWe present an 11-year-old male with medulloblastoma, who harbors a de novo PHOX2B germline mutation as detected by whole exome sequencing (WES). Family history was negative. Sanger sequencing confirmed this mutation in peripheral blood, hair bulbs, urine and saliva. Identification of novel germline mutations is beneficial for childhood cancer screening.ConclusionsThis case revealed a de novo PHOX2B germline mutation as a potential cause of medulloblastoma in a child and suggests familial germline variant screening is useful when an affected family is considering having a second child.

Highlights

Medulloblastoma is a malignant tumor of the cerebellum that is most common in childhood, characterized by highly malignant manifestations including rapid tumor growth, high recurrence rate, and poor overall survival [1]
The pathogenic roles of PHOX2B mutations have been published in the ClinVar database, but few reports exist on de novo germline mutations associated with childhood medulloblastoma development
By using whole exome sequencing (WES, the NovaSeq 6000 Sequencing System, Illumina) technology and Sanger sequencing validation, we report the case of a child with a de novo c.765_779 deletion of PHOX2B as a contributor to the risk of medulloblastoma

Summary

Introduction

Medulloblastoma is a malignant tumor of the cerebellum that is most common in childhood, characterized by highly malignant manifestations including rapid tumor growth, high recurrence rate, and poor overall survival [1]. Six germline mutations: APC, BRCA2, PALB2, PTCH1, SUFU, and TP53, were reported to be responsible for 6% of medulloblastoma cases [3]. The pathogenic roles of PHOX2B mutations have been published in the ClinVar database, but few reports exist on de novo germline mutations associated with childhood medulloblastoma development. By using whole exome sequencing (WES, the NovaSeq 6000 Sequencing System, Illumina) technology and Sanger sequencing validation, we report the case of a child with a de novo c.765_779 deletion of PHOX2B as a contributor to the risk of medulloblastoma

Methods and results

Findings

Discussion