The authors described four patients with a novel 1p36.11 microduplication syndrome involving the ARID1A gene. The four patients shared a strikingly similar phenotype that included intellectual disability and microcephaly.
The authors reported eight subjects from six families with loss of function variants in ZNF462. These individuals had overlapping phenotypes that included ptosis, metopic ridging, craniosynostosis, dysgenesis of the corpus callosum, and developmental delay.
The authors reported deletions that generated chimeric ATAD3B/ATAD3A fusion genes in individuals from four unrelated families with fatal congenital pontocerebellar hypoplasia, whereas a case with genomic rearrangements affecting the ATAD3C/ATAD3B genes on one allele and ATAD3B/ATAD3A genes on the other displayed later-onset encephalopathy with cerebellar atrophy, ataxia and dystonia.
In two different articles, the first families carrying recessive variants in the MSTO1 gene were reported. In a first article, compound heterozygous mutations were identified in two sisters and in an unrelated singleton case, who presented a multisystem complex phenotype mainly characterised by myopathy and cerebellar ataxia. In a second article, the authors identified a mutation of MSTO1 in patients with minor physical abnormalities, myopathy, ataxia, and neurodevelopmental impairments. Lactate stress test and myopathological results suggested mitochondrial dysfunction.
The authors reported biallelic P4HA1 mutations in a family. Two siblings presented with a congenital-onset disorder of connective tissue, manifesting as early-onset joint hypermobility, joint contractures, muscle weakness and bone dysplasia as well as high myopia, with evidence of clinical improvement of motor function over time in the surviving patient.
The authors performed exome sequencing in a patient and his unrelated unaffected parents to identify the genetic aetiology of a syndrome characterised by neonatal diabetes, sensorineural deafness, and congenital cataracts. Further testing was performed in 311 patients with diabetes diagnosed before 1 year of age in whom all known genetic causes had been excluded. The authors identified 5 patients, including the initial case, with three heterozygous missense mutations in WFS1 (4/5 confirmed de novo). They had diabetes diagnosed before 12 months (2 before 6 months) (5/5), sensorineural deafness diagnosed soon after birth (5/5), congenital cataracts (4/5), and hypotonia (4/5).
The authors identified mutations located in POLR3A to be a frequent cause of hereditary spastic paraplegia and cerebellar ataxia. First, whole-exome sequencing findings in a recessive spastic ataxia family revealed variants in POLR3A. Next, the authors screened a cohort of hereditary spastic paraplegia and cerebellar ataxia cases (n = 618) for mutations in POLR3A and identified compound heterozygous POLR3A mutations.
Twelve individuals of consanguineous Bedouin kindred presented with autosomal recessive progressive spastic paraplegia evident as of age 0-24 months, with spasticity of lower limbs, hyperreflexia, toe walking and equinus deformity. Kyphoscolisois was evident in older patients. Most had atrophy of the lateral aspects of the tongue and few had intellectual disability. Nerve conduction velocity, electromyography and head and spinal cord magnetic resonance imaging were normal in tested subjects. Muscle biopsy showed occasional central nuclei and fiber size variability with small angular fibers. Whole-exome sequencing identified a single homozygous variant in KY, segregating in the family as expected and not found in 190 Bedouin controls.
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:
The European Journal of Human Genetics has published one updated 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 counseling of patients and families with specific inherited conditions.
Five updated GeneReviews have been published for: