The authors reported the clinical and molecular cytogenetic characterisation of four unrelated patients from France and Spain, carrying 2p14 microdeletions and presenting with intellectual disability and dysmorphism. Some patients also developed sensorineural hearing loss, progressive cardiomyopathy, retinopathy and mild midline abnormalities.
The authors identified biallelic COL3A1 variants in two unrelated families. A 3-year-old female presented developmental, bilateral clubfoot, joint laxity, and dysmorphic facial features. At the age of 2 years she developed an aneurysmal brain haemorrhage. Cerebral MRI showed a peculiar pattern of profound cerebral abnormalities including bilateral frontoparietal polymicrogyria of the cobblestone variant. In the second family, the two affected siblings showed cobblestone-like cortical malformation, cerebellar cysts, white matter abnormalities, developmental delay, and seizures. To date, three further families have been reported with biallelic variants of this gene and specific structural brain anomalies in all, and a severe Ehlers-Danlos syndrome phenotype in some.
The authors reported seven individuals with distinct de novo missense RAC1 mutations and varying degrees of developmental delay, brain malformations, and additional phenotypes. Four individuals were microcephalic, with head circumferences between -2.5 to -5 SD. In contrast, two individuals were macrocephalic with head circumferences of +4.16 and +4.5 SD. One individual had head circumference in the normal range.
In seven unrelated affected individuals, all suffering from developmental regression starting at 2.5-7 years, the authors identified a heterozygous variant in UBTF. Patients presented with developmental delay and cerebellar atrophy.
The authors reported that variants in TRAPPC12 resulted in progressive childhood encephalopathy. Three individuals from two unrelated families had either a homozygous deleterious variant or compound-heterozygous variants. The clinical phenotypes of the three individuals were strikingly similar: severe disability, microcephaly, hearing loss, spasticity, and characteristic brain imaging findings. Fibroblasts derived from all three individuals showed a fragmented Golgi that could be rescued by expression of wild-type TRAPPC12.
In five separate families, the authors identified nine individuals affected by a previously unidentified syndrome characterised by growth retardation, spine malformation, facial dysmorphism, and developmental delay. Using homozygosity mapping, array CGH, and exome sequencing, they uncovered bi-allelic loss-of-function CDK10 mutations segregating with this disease.
The authors described heterozygous dominant mutations in GRM1. These mutations were associated with a novel type of adult-onset cerebellar ataxia or spinocerebellar ataxia type 44.
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.
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