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Mutations in CASK are associated with X-linked mental retardation (XLMR) but, interestingly, some individuals also present with congenital nystagmus and the mutations carried by these individuals map to C-terminal region of CASK (8, 27).
DS individuals also present with reduced brain size, brain weight, brain volume, neuronal density, and neuronal distribution with neurons that are characterized by shorter dendritic spines, reduced dendritic arborization and synaptic abnormalities [ 6– 8].
GIST in NF1 individuals also present typically in the small bowel with spindle-cell morphology, are found in men and women at a younger median age than KIT/ PDGFRA mutant GIST, and are often multifocal [ 17, 18].
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Some individuals also presents with the so called putative latency program (latency 0), in which no detectable latent gene expression is detected [10].
Clinical severity was not reported in detail, but the affected individuals also presented with progressive sensorineural high-frequency hearing loss.
The reason for excluding opioid-dependent individuals also presenting with benzodiazepine and alcohol dependence was based on the results of several studies which have shown an increased risk of overdose associated with benzodiazepine use and alcohol use [ 13].
Classically, the highest frequency and magnitude of proliferation are found in HAM/TSP [ 31, 32] although a lower frequency of infected asymptomatic individuals also presents similar levels of proliferation [ 13, 14].
Affected individuals can also present with heart defects, cleft lip and/or palate, hearing impairment and eye anomalies.
From our surveys, we can anticipate that more than half of these individuals will also present with chronic kidney disease (3).
Individuals with RTT also present with autonomic abnormalities (Julu et al., 1997), which raises the question of whether autonomic nervous system imbalance might be causing the cardiac abnormalities.
18% of individuals with RTT also present with long QT (LQT), a heart rhythm abnormality associated with a prolongation of the heart QT interval that can lead to sudden death.
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