The authors reported nine children with MYT1L variants (four loss of function and five missense). All patients presented with intellectual disability and obesity.
The authors reported a pair of siblings carrying a homozygous missense mutation in EEF1A2 who exhibited global developmental delay, failure to thrive, dilated cardiomyopathy and epilepsy, ultimately leading to death in early childhood. A third sibling also died of a similar presentation, but DNA was unavailable to confirm the mutation.
The authors reported a novel variant in GPKOW. This variant segregated with affected and carrier status in a multigenerational family with an X-linked perinatal lethal condition characterised by severe microcephaly and intrauterine growth restriction.
The authors reported two siblings with progressive microcephaly with hypomyelination, intractable epilepsy, and spasticity. Whole-exome sequencing identified that the affected individuals were compound heterozygous for mutations in AARS gene.
The authors described a three-generation family affected with developmental glaucoma, myopia, and/or retinal defects associated with variable craniofacial/dental, auditory, brain, renal, and limb anomalies. Whole-exome sequencing identified a heterozygous allele in ADAMTSL1.
The authors showed that a missense mutation of NLRP3 caused autosomal-dominant sensorineural hearing loss in two unrelated families. The hearing loss in three affected members of one family improved or completely resolved after treatment with IL-1β blockade therapy. Mutations of NLRP3 may cause hearing loss by local autoinflammation within the inner ear.
The authors sought to identify the cause of two new diseases in two unrelated Finnish kindreds with variable symptoms of immunodeficiency and autoinflammation. In all affected subjects, they detected novel heterozygous variants in NFKB1. Symptoms in variant carriers differed depending on the mutation. Patients with a p.H67R substitution had antibody deficiency and experienced autoinflammatory episodes, including aphthae, gastrointestinal disease, febrile attacks, and small-vessel vasculitis characteristic of Behçet disease. Patients with a p.R157X stop-gain experienced hyperinflammatory responses to surgery and showed enhanced inflammasome activation. They had postoperative deep necrotising cellulitis with abscesses, fever, neutrophilia, and increased inflammatory markers that required
prolonged intensive care and multiple surgical revisions.
The authors characterised a three-generation family presenting with skin anomalies, impaired scarring, night blindness, muscle weakness, osteoarthritis, joint and internal organs ligaments laxity, malabsorption syndrome and hypothyroidism. Patients presented with a heterozygous LAMA5 mutation.
The authors showed that de novo NFE2L2 mutations caused an early onset multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms in four patients. The unique combination of white matter lesions, hypohomocysteinaemia and increased G-6-P-dehydrogenase activity will facilitate early diagnosis and therapeutic intervention of this novel disorder.
EuroGentest, the EU-funded Network of Excellence for genetic testing, has developed disease-specific points to consider regarding clinical indications for genetic testing - the Clinical Utility Gene Cards (CUGCs). These documents provide clinicians and clinical geneticists with guidance on genetic testing for specific conditions in real settings of clinical genetic services. Published in the European Journal of Human Genetics and also available on the Orphanet website, the CUGCs focus on Mendelian diseases.
The European Journal of Human Genetics has published one new Clinical Utility Gene Card for:
GeneReviews are expert-authored, peer-reviewed disease descriptions ("chapters") presented in a standardised format and focused on clinically relevant and medically actionable information on the diagnosis, management, and genetic counselling of patients and families with specific inherited conditions.
Three updated GeneReviews have been published for: