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Case Reports
. 2020 Mar;8(3):e1144.
doi: 10.1002/mgg3.1144. Epub 2020 Jan 27.

First maternal uniparental disomy for chromosome 2 with PREPL novel frameshift mutation of congenital myasthenic syndrome 22 in an infant

Ping Zhang  1   2 , Bingbing Wu  1   2 , Yulan Lu  1   2 , Qi Ni  1   2 , Renchao Liu  1   2 , Wenhao Zhou  1   2   3 , Huijun Wang  1   2
Affiliations
Case Reports

First maternal uniparental disomy for chromosome 2 with PREPL novel frameshift mutation of congenital myasthenic syndrome 22 in an infant

Ping Zhang et al. Mol Genet Genomic Med. 2020 Mar.

Abstract

Background: Congenital myasthenic syndrome 22 (CMS22) is a rare autosomal recessive disorder due to isolated PREPL deficiency and characterized by neonatal hypotonia, muscular weakness, and feeding difficulties. Eight such cases have already been reported, while maternal uniparental disomy with a PREPL pathogenic mutation has never been involved.

Methods: Trio whole-exome sequencing (WES), comparative genomic hybridization microarray (arry-CGH), and Sanger sequencing were performed on a 6-month-old girl with severe neonatal hypotonia and feeding difficulties. Also, the phenotype and genotype of reported CMS22 patients were reviewed.

Results: In this female infant, we identified a novel homozygous frameshift mutation in PREPL (c.1282_1285delTTTG, p.Phe428Argfs*18) by trio-WES. Sanger sequencing confirmed that her mother was heterozygous and her father was normal. Trio-WES data showed that 96.70% (1668/1725) variants on chromosome 2 were homozygous and maternally inherited, suggesting maternal uniparental disomy of chromosome 2 [UPD(2)mat]. Array-CGH did not show copy number variants (CNVs) but revealed complete UPD(2).

Conclusion: To date, nine patients with CMS22 have been reported including our patient, and we report the youngest and the first UPD(2)mat with PREPL novel homozygous pathogenic mutation case, which expand the mutation spectrum of PREPL gene.

Keywords: PREPL gene; congenital myasthenic syndrome 22; pyridostigmine treatment; uniparental disomy.

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Conflict of interest statement

The authors declare no potential conflict of interest.

Figures

Figure 1
Figure 1
Results of genetic tests in our patient. (a) Trio‐WES identifies that 96.70% (1668/1725) variants on chromosome 2 are homozygous and inherited from the mother, suggesting that the proband has UPD(2)mat. (b) A novel homozygous frameshift variant on PREPL (c.1282_1285delTTTG) is detected in the proband. Her mother is heterozygous and her father is normal. (c) The variant is confirmed by Sanger sequencing. D Array‐CGH identifies UPD(2) by showing the LOH across the whole chromosome 2
Figure 2
Figure 2
Summary of pathogenic variants and gross deletions in PREPL. (a) Nine truncating mutations on PREPL. The red shows the novel frameshift mutation in our patient. (b) The size and location of the six reported gross deletions in CMS22 patients
See this image and copyright information in PMC

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