Adult-onset leukoencephalopathy with homozygous LAMB1 missense mutation

ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia

Objective To identify the clinical characteristics and genetic etiology of a family affected with hereditary spastic paraplegia (HSP). Methods Clinical, genetic, and functional analyses involving genome-wide linkage coupled to whole-exome sequencing in a consanguineous family with complicated HSP. Results A homozygous missense mutation was identified in the ACO2 gene (c.1240T>G p.Phe414Val)...

Intellectual disability associated with a homozygous missense mutation in THOC6

BACKGROUND We recently described a novel autosomal recessive neurodevelopmental disorder with intellectual disability in four patients from two related Hutterite families. Identity-by-descent mapping localized the gene to a 5.1 Mb region at chromosome 16p13.3 containing more than 170 known or predicted genes. The objective of this study was to identify the causative gene for this rare disorder....

Homozygous NOTCH3 null mutation and impaired NOTCH3 signaling in recessive early-onset arteriopathy and cavitating leukoencephalopathy

Notch signaling is essential for vascular physiology. Neomorphic heterozygous mutations in NOTCH3, one of the four human NOTCH receptors, cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Hypomorphic heterozygous alleles have been occasionally described in association with a spectrum of cerebrovascular phenotypes overlapping CADASIL, but...

LAMA2 mutations in adult-onset muscular dystrophy with leukoencephalopathy.

Clinical and genetic characterization of adult‐onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation

BACKGROUND AND PURPOSE The clinical characteristics of colony stimulating factor 1 receptor (CSF1R) related adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) have been only partially elucidated. METHODS Clinical data from CSF1R mutation carriers who had been seen at our institutions or reported elsewhere were collected and analysed using a specific investigation ...