Novel PHOX2B germline mutation in childhood medulloblastoma: a case report.
Ontology highlight
ABSTRACT: Background
Medulloblastoma is an aggressive brain tumor mostly found in children, few studies on pathogenic germline mutations predisposing this disease was reported.Case presentation
We 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.Conclusions
This 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.
SUBMITTER: Ke C
PROVIDER: S-EPMC7816394 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Novel PHOX2B germline mutation in childhood medulloblastoma: a case report.
Ke Caiping C Shi Xiaoshun X Chen Allen Menglin AM Li Chaoming C Jiang Bifeng B Huang Kailing K Zheng Zhouxia Z Liu Yanhui Y Chen Zhuona Z Luo Yingjun Y Lin Huaming H Zhang Jiexia J
Hereditary cancer in clinical practice 20210119 1
<h4>Background</h4>Medulloblastoma is an aggressive brain tumor mostly found in children, few studies on pathogenic germline mutations predisposing this disease was reported.<h4>Case presentation</h4>We 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 ...[more]
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Project description:BackgroundBilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing's syndrome (CS). BMAH is predominantly believed to be caused by two mutations, a germline and somatic one, respectively, as described in the two-hit hypothesis. In many familial cases of BMAH, mutations in armadillo repeat containing 5 (ARMC5), a putative tumor suppressor gene, are thought to induce the disorder. The objective of this study was to report a case in which the patient presented with BMAH induced by a novel heterozygous germline ARMC5 mutation (c. 517C > T, p. Arg173*) alone rather than a two-hit mutation.Case presentationA 51-year-old woman was identified with masses in the bilateral adrenals. Serum cortisol levels were increased significantly both in the morning (08:00 AM) and late at night (24:00 AM), while plasma adrenocorticotropic hormone was normal. The patient underwent a left adrenalectomy and histopathology substantiated the BMAH diagnosis. WES of the germline DNA discovered a novel heterozygous germline ARMC5 mutation (c. 517C > T, p. Arg173*) and in silico analysis predicted that the mutation significantly impaired protein function, resulting in inactivated ARMC5. Subsequently, WES of the tumor specimen identified 79 somatic single nucleotide polymorphisms (SNPs)/insertion-deletion (indel) mutations, including 32 missense/nonsense/splice/stop-loss mutations. None of these mutations were CS-related.ConclusionsA novel germline ARMC5 mutation (c. 517C > T, p. Arg173*) was identified that induced BMAH alone without a second mutation. ARMC5 sequencing may improve the identification of clinical forms of BMAH and allow earlier diagnosis of this disease.
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