Rare Variants in MME , Encoding Metalloprotease Neprilysin, Are Linked to Late-Onset Autosomal-Dominant Axonal Polyneuropathies

Proteins linked to autosomal dominant and autosomal recessive disorders harbor characteristic rare missense mutation distribution patterns.

The role of rare missense variants in disease causation remains difficult to interpret. We explore whether the clustering pattern of rare missense variants (MAF < 0.01) in a protein is associated with mode of inheritance. Mutations in genes associated with autosomal dominant (AD) conditions are known to result in either loss or gain of function, whereas mutations in genes associated with autoso...

MME mutation in dominant spinocerebellar ataxia with neuropathy (SCA43)

OBJECTIVE To identify the causative gene mutation in a 5-generation Belgian family with dominantly inherited spinocerebellar ataxia and polyneuropathy, in which known genetic etiologies had been excluded. METHODS We collected DNA samples of 28 family members, including 7 living affected individuals, whose clinical records were reviewed by a neurologist experienced in ataxia. We combined linka...

Adult-onset autosomal dominant spastic paraplegia linked to a GTPase-effector domain mutation of dynamin 2

BACKGROUND Hereditary Spastic Paraplegia (HSP) represents a large group of clinically and genetically heterogeneous disorders linked to over 70 different loci and more than 60 recognized disease-causing genes. A heightened vulnerability to disruption of various cellular processes inherent to the unique function and morphology of corticospinal neurons may account, at least in part, for the genet...

Frontometaphyseal dysplasia: autosomal dominant or X-linked?

The clinical and radiographic manifestations in a 45-year-old male with frontometaphyseal dysplasia (FMD) are documented and depicted. Deafness and degenerative osteoarthropathy in weight-bearing joints were the main clinical problems. Widespread patchy cranial sclerosis was reminiscent of Paget's disease, while digital deformity resembled rheumatoid arthritis. On the basis of a review and tabu...

Adult-onset autosomal dominant leukodystrophy: linking nuclear envelope to myelin.