Dataset Information

De novo ATP1A2 variants in two Chinese children with alternating hemiplegia of childhood upgraded the gene-disease relationship and variant classification: a case report.

ABSTRACT:

Background

ATP1A2 gene mutation has been indicated to cause alternating hemiplegia of childhood (AHC); however, limited evidence supports this relationship so far.

Case presentation

We reported two Chinese patients with de novo ATP1A2 variants (c.970G>A and c.889G>A). Both patients presented with episodes of alternating hemiplegia, seizures and mild developmental delay. Brain magnetic resonance imaging revealed abnormal signals in both patients.

Conclusions

The new genetic evidence we reported here strengthened the gene-disease relationship, and the gene curation level between ATP1A2 and AHC became "Moderate" following the ClinGen Standard Operation Procedure. Consequently, the two variants can be reclassified as likely pathogenic.

SUBMITTER: Huang D

PROVIDER: S-EPMC8017680 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

De novo ATP1A2 variants in two Chinese children with alternating hemiplegia of childhood upgraded the gene-disease relationship and variant classification: a case report.

Huang Danping D Liu Min M Wang Hongying H Zhang Bingbing B Zhao Dongjing D Ling Weihao W Wang Manli M Feng Jun J Shen Yiping Y Chen Xuqin X

BMC medical genomics 20210401 1

<h4>Background</h4>ATP1A2 gene mutation has been indicated to cause alternating hemiplegia of childhood (AHC); however, limited evidence supports this relationship so far.<h4>Case presentation</h4>We reported two Chinese patients with de novo ATP1A2 variants (c.970G>A and c.889G>A). Both patients presented with episodes of alternating hemiplegia, seizures and mild developmental delay. Brain magnetic resonance imaging revealed abnormal signals in both patients.<h4>Conclusions</h4>The new genetic ...[more]

PMID: 33794876

Similar Datasets

Project description:BackgroundPathogenic variants of ATP1A2 (OMIM ID: 182340) are usually associated with familial hemiplegic migraine type 2 (FHM-2), alternating hemiplegia of childhood (AHC), early infantile epileptic encephalopathy (EIEE), transient cytotoxic edema, and so on. Here, we present a novel heterozygous ATP1A2 variant in a girl with alternating hemiplegia, febrile seizures, developmental delay (which subsequently subsided), and MELAS-like syndrome (as indicated by brain MRI). The patient did not experience migraine with aura.MethodsThe patient was an 8-year-old girl with normal growth and development. Beginning from the age of 3 years and 8 months, the patient experienced several episodes of alternating limb paralysis. The episodes were accompanied by the appearance of MELAS-like findings on brain MRI, which corresponded to the hemiplegia. There were abnormal linear signals in the cerebral cortex on the opposite side of the hemiplegic limb. Each time the patient recovered from hemiplegia, and each time MRI showed no lesions remained after recovery. No obvious abnormality was found in other examinations. Finally, the patient underwent whole-exome sequencing (WES).ResultsWES revealed a novel and de novo heterozygous variant in the ATP1A2 (NM_000702.3) c.335C>A:p.Ala112Asp (not previously reported). We examined the variant position in the 3D protein structure and found that a missense mutation at this site is a nonconservative substitution. The variation is nonpolymorphic. It occurs at a very low frequency in the population, and its ACMG classification is likely pathogenic.ConclusionAt present, there are limited reports of mutations in the ATP1A2 gene causing AHC. This is the first case of brain MRI showing MELAS-like imaging in an AHC patient, and more cases are needed for verification. Early genetic testing and family screening can aid in the diagnosis and treatment of genetic diseases. The relationship between ATP1A2 gene mutation genotype and clinical phenotype needs to be further studied.

Dataset Information

De novo ATP1A2 variants in two Chinese children with alternating hemiplegia of childhood upgraded the gene-disease relationship and variant classification: a case report.

Background

Case presentation

Conclusions

Publications

De novo ATP1A2 variants in two Chinese children with alternating hemiplegia of childhood upgraded the gene-disease relationship and variant classification: a case report.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets