A homozygous GRIN1 null variant causes a more severe phenotype of early infantile epileptic encephalopathy.

Pathogenic variants in glutamate receptor, ionotropic, NMDA-1 (GRIN1) cause an autosomal dominant or recessive neurodevelopmental disorder with global developmental delay, with or without seizures (AD or AR GRIN1-NDD). Here, we describe a novel homozygous canonical splice site variant in GRIN1 in a 12-month-old boy with early infantile epileptic encephalopathy and severe global developmental delay. This represents only the second family with a homozygous predicted-null variant in GRIN1 reported to date. We review the published literature on AR GRIN1-NDD and find that the phenotype in our patient is much more severe than those seen with homozygous missense variants. A similarly severe phenotype of intractable epilepsy and infantile death has only been reported in one other family with a homozygous nonsense variant in GRIN1. We, therefore, propose that biallelic predicted-null variants in GRIN1 can cause a markedly more severe clinical phenotype than AR GRIN1-NDD caused by missense variants.

Remarkably Few Sputum Cultures from People with Parkinson's Disease during Hospital In-Patient Admission.

Although respiratory tract infections can be a common complication in people with Parkinson's disease (PD), there is little published data on the nature of such infections in this patient group. We wished to investigate whether sputum samples were being taken from PD patients in order to establish whether an infection was present and if so which bacteria were responsible for the infection. We recorded the number of positive sputum samples taken from admission to North Tyneside General Hospital in North-East England across a ten-year period from June 2001 to June 2011. Of 643 in-patient episodes involving people with PD, positive sputum samples were recorded for only 12 episodes (1.9%) in eight patients. All patients were in early stage disease. In all admissions to the NHS Trust running the hospital, there were 23,069 sputum cultures from 1,056,693 in-patient episodes (2.2%). Our findings may reflect the difficultly of expectorating in many people with PD, particularly in late-stage disease. Since people with PD are especially vulnerable to respiratory tract infections, clinicians need to ensure that, where possible, a sputum sample is obtained from people with PD when clinically indicated.