Whole-exome sequencing in fetuses with central nervous system abnormalities

Reches, Adi; Hiersch, Liran; Simchoni, Sharon; Barel, Dalit; Greenberg, Rotem; Ben-Sira, Liat; Malinger, G.; Yaron, Yuval

doi:10.1038/s41372-018-0199-3

Cited by 39 publications

(40 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The clinical presentation was characterized by an older onset age compared with previously reported VRK1 neuropathy patients, who usually manifest in childhood through early adulthood, but not later than the end of the third decade . No upper motor neuron signs, cognitive impairment, abnormal brain imaging findings, or microcephaly were noted in our patients, in contrast to other reported cases of VRK1 mutations . However, mild sensory symptoms (probably related to small fiber loss) and respiratory insufficiency were present in one.…”

Section: Discussioncontrasting

confidence: 52%

“…Several other mutations have been previously reported in VRK1 ‐related disorders in various populations, for example the nonsense mutation c.1072C>T (p.Arg358Ter) in the Ashkenazi Jewish origin . The currently identified mutation is located in the first nucleotide of the last (13th) exon of the gene, changing amino acid number 387 of 396 in the protein (Figure ).…”

Section: Discussionmentioning

confidence: 99%

“…Schematic illustration of the VRK1 protein and the mutations identified within it (wide arrow denotes the currently reported mutation) . Protein domains and their positions are shown below…”

Section: Discussionmentioning

confidence: 99%

“…Among these are motor neuron disease (including SMA) in children with or without pontocerebellar hypoplasia, motor and sensory axonal neuropathy plus microcephaly, dHMN and dHMN associated with upper motor neuron signs, early onset amyotrophic lateral sclerosis, and adult‐onset dSMA . In other cases, pontocerebellar hypoplasia with intellectual disability, primary micocephaly or brain abnormalities in the prenatal setting were reported.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Identification of a homozygous VRK1 mutation in two patients with adult‐onset distal hereditary motor neuropathy

et al. 2020

View full text Add to dashboard Cite

Background Adult‐onset hereditary motor neuropathies are caused by mutations in multiple genes. Mutations within the vaccinia‐related kinase 1 (VRK1) gene were associated with a wide spectrum of recessively inherited motor neuropathies, characterized by childhood to early adulthood age of onset and an occasionally non‐lower motor neuron involvement. Methods We describe two patients with adult‐onset (aged 48 and 40 years) length‐dependent motor neuropathy from unrelated consanguineous families of Moroccan Jewish descent. One also demonstrated mild nocturnal respiratory difficulty and sensory symptoms. Whole‐exome sequencing (WES) was performed. Results A homozygous mutation in VRK1 (c.1160G>A (p.Arg387His)), shared by both patients, was identified. This rare mutation segregated with the disease in the two families, and was absent in 120 controls of Jewish Moroccan origin. Conclusions Our findings support VRK1 as a causative gene for adult‐onset distal hereditary motor neuropathy, and indicate its relevance for evaluation of individuals with similar motor impairment.

show abstract

Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Identification of a homozygous VRK1 mutation in two patients with adult‐onset distal hereditary motor neuropathy

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Among these are motor neuron disease (including SMA) in children with or without pontocerebellar hypoplasia, [6][7][8][9] motor and sensory axonal neuropathy plus microcephaly, 10 dHMN 11,12 and dHMN associated with upper motor neuron signs, 13 early onset amyotrophic lateral sclerosis, 14 and adult-onset dSMA. 7,15 In other cases, pontocerebellar hypoplasia with intellectual disability, 16 primary micocephaly 17 or brain abnormalities in the prenatal setting 18 were reported.…”

mentioning

confidence: 99%

Examination of the human motor endplate after brachial plexus injury with two‐photon microscopy

et al. 2019

View full text Add to dashboard Cite

Introduction After traumatic nerve injury, neuromuscular junction remodeling plays a key role in determining functional outcomes. Immunohistochemical analyses of denervated muscle biopsies may provide valuable prognostic data regarding clinical outcomes to supplement electrodiagnostic studies. Methods We performed biopsies on nonfunctioning deltoid muscles in two patients after gunshot wounds and visualized the neuromuscular junctions using two‐photon microscopy with immunohistochemistry. Results Although the nerves in both patients showed evidence of acute Wallerian degeneration, some of the motor endplates were intact but exhibited significantly decreased surface area and volume. Both patients exhibited substantial recovery of motor function over several weeks postinjury. Discussion Two‐photon microscopic assessment of neuromuscular junction integrity and motor endplate morphometry in muscle biopsies provided evidence of partial sparing of muscle innervation. This finding supported the clinical judgment that eventual recovery would occur. With further study, this technique may help to guide operative decisionmaking after traumatic nerve injuries.

show abstract

Prenatal diagnosis of a likely pathogenic variant in ZBTB18: Natural evolution of fetal phenotype including the long bones and corpus callosum

Birnbaum

Markovitch

Biron‐Shental

et al. 2021

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Pathogenic variants in ZBTB18 gene have been described only postnatally with a variable phenotypic spectrum that includes intellectual disability, microcephaly, hypotonia, poor growth, corpus callosum abnormalities, seizures, and dysmorphic facial features. These features overlap with the phenotype of 1q43-q44 deletion syndrome (OMIM #612337). There are several genes within the 1q43-q44 deletion region, and ZBTB18 is of particular interest due to its known involvement in neuronal differentiation and migration. We describe here a fetus presenting with an intrauterine growth restriction, diminished long bones growth, single umbilical artery, and a short corpus callosum. On mid pregnancy ultrasound, all biometric parameters including the corpus callosum were relatively small but still within the normal range. Only a targeted follow-up during the third trimester, including neurosonographic and MRI exams, revealed the full extent of the malformation, leading to amniocentesis and a genetic workup that led to the identification of a de novo likely pathogenic variant in ZBTB18 gene. This is the first description of the evolving phenotype of a ZBTB18-related disorder in a fetus, which emphasizes the challenging diagnosis of subtle findings, that mandates a high level of clinical suspicion and a targeted follow-up throughout pregnancy.

show abstract

Whole-exome sequencing in fetuses with central nervous system abnormalities

Abstract: Whole-exome sequencing may improve prenatal diagnosis in fetuses with CNS abnormalities.

Cited by 39 publications

References 30 publications

Identification of a homozygous VRK1 mutation in two patients with adult‐onset distal hereditary motor neuropathy

Identification of a homozygous VRK1 mutation in two patients with adult‐onset distal hereditary motor neuropathy

Examination of the human motor endplate after brachial plexus injury with two‐photon microscopy

Prenatal diagnosis of a likely pathogenic variant in ZBTB18: Natural evolution of fetal phenotype including the long bones and corpus callosum

Contact Info

Product

Resources

About