Rare Case of Female with Pelizaeus Mertzbacher Disease Due to Deletion of Proteolipid Protein 1

Kinoshita, Masanosuke; Roston, William

doi:10.31729/jnma.3824

Cited by 2 publications

(3 citation statements)

References 3 publications

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“…As shown in Table 1, we analysed the genotype-phenotype correlations of these patients with CNV deletions in chromosome Xq22.1-q22.3. Among them, the phenotype of female cases mainly include severe mental or physical limitations [9,[12][13][14][15][16][17]27]. But so far, only one 4-year-old female of Xq22.1 → qter deletion had a normal phenotype [32].…”

Section: Discussionmentioning

confidence: 99%

Familial 5.29 Mb deletion in chromosome Xq22.1–q22.3 with a normal phenotype: a rare pedigree and literature review

Hui-Hui

Zhang

et al. 2023

BMC Med Genomics

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Background Xq22.1–q22.3 deletion is a rare chromosome aberration. The purpose of this study was to identify the correlation between the phenotype and genotype of chromosome Xq22.1–q22.3 deletions. Methods Chromosome aberrations were identified by copy number variation sequencing (CNV-seq) technology and karyotype analysis. Furthermore, we reviewed patients with Xq22.1–q22.3 deletions or a deletion partially overlapping this region to highlight the rare condition and analyse the genotype–phenotype correlations. Results We described a female foetus who is the “proband” of a Chinese pedigree and carries a heterozygous 5.29 Mb deletion (GRCh37: chrX: 100,460,000–105,740,000) in chromosome Xq22.1–q22.3, which may affect 98 genes from DRP2 to NAP1L4P2. This deletion encompasses 7 known morbid genes: TIMM8A, BTK, GLA, HNRNPH2, GPRASP2, PLP1, and SERPINA7. In addition, the parents have a normal phenotype and are of normal intelligence. The paternal genotype is normal. The mother carries the same deletion in the X chromosome. These results indicate that the foetus inherited this CNV from her mother. Moreover, two more healthy female family members were identified to carry the same CNV deletion through pedigree analysis according to the next-generation sequencing (NGS) results. To our knowledge, this family is the first pedigree to have the largest reported deletion of Xq22.1–q22.3 but to have a normal phenotype with normal intelligence. Conclusions Our findings further improve the understanding of the genotype–phenotype correlations of chromosome Xq22.1–q22.3 deletions.This report may provide novel information for prenatal diagnosis and genetic counselling for patients who carry similar chromosome abnormalities.

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Section: Discussionmentioning

confidence: 99%

Familial 5.29 Mb deletion in chromosome Xq22.1–q22.3 with a normal phenotype: a rare pedigree and literature review

Hui-Hui

Zhang

et al. 2023

BMC Med Genomics

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“…Based on the large size of this duplication and its gene content, this is a pathogenic copy number variant (CNV) in males. Clinical manifestations in female carriers depend on the X inactivation status [8]. Since the X inactivation status was unknown, this CNV was classified as a variant of uncertain significance (VUS).…”

Section: Genetic Investigationsmentioning

confidence: 99%

“…VariousPLP1 mutations, including duplications, point mutations, and deletions, lead to oligodendrocyte dysfunction in patients with PMD [2]. PMD is classified according to its severity, with the mild form of PMD the most common, typically presenting with initial symptoms of hypotonia, nystagmus, ataxia and delayed development of motor skills [3,8]. As an X-linked disease, PMD should in theory only affect males [4].…”

Section: Introductionmentioning

confidence: 99%

Pelizaeus Merzbacher Disease in a Female due to Proteolipid Protein 1 duplication: A Case Report

Almobarak¹

2021

JNNS

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Pelizaeus–Merzbacher disease (PMD) is a rare X-linked central nervous system disease involving the proteolipid protein 1 (PLP1) gene on Xq22.1. PMD patients’ commonly exhibit signs including nystagmus, hypotonia, and developmental delay. We report a female case of mild spectrum phenotypic expression of PMD attributable to a de novo Copy Number Variant (CNV) change. A two and half-year-old girl presented to our clinic with hypotonicity. She had apneic spells at birth, and was diagnosed to have nystagmus when she was 3 months old. In addition, she presented with delayed motor development including poor head control and inability to sit independently at 6 months of age, eventually standing with support at 20 months, and a prominent wide-based gait at 24 months. MRI head revealed diffuse, markedly delayed myelination, with a reduction in white matter volume. A chromosomal microarray testing indicated that patient carries an Xq22.1 q23 duplication of uncertain significance, of which the PLP1 is fully duplicated. Parental studies were normal. X-inactivation study was normal. Therefore, our case represents a phenotypic expression of PMD due to de novo mutation, a rare occurrence in a female.

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Rare Case of Female with Pelizaeus Mertzbacher Disease Due to Deletion of Proteolipid Protein 1

Cited by 2 publications

References 3 publications

Familial 5.29 Mb deletion in chromosome Xq22.1–q22.3 with a normal phenotype: a rare pedigree and literature review

Familial 5.29 Mb deletion in chromosome Xq22.1–q22.3 with a normal phenotype: a rare pedigree and literature review

Pelizaeus Merzbacher Disease in a Female due to Proteolipid Protein 1 duplication: A Case Report

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