A Dominant Form of Neuronal Ceroid-Lipofuscinosis

Neuronal Ceroid Lipofuscinosis in Rambouillet Sheep: Characterization of the Clinical Disease

“…In one exception, the adult human form of NCL (Kuffs disease), an autosomal dominant mode of transmission has been suggested. 21 The presence of NCL in both male and female progeny of a group of related, phenotypically normal Rambouillet rams and ewes, associated with consanguineous matings between such rams and ewes, is supportive of an autosomal recessive mode of inheritance. Also, experimental breeding of Rambouillet sires and dams with known genotypes produced affected lambs with predicted frequency consistent with an autosoma1 recessive trait.…”

Lysosomal storage disease in the brain: mutations of the β-mannosidase gene identified in autosomal dominant nystagmus

“…The accumulated substrate(s) of the defective enzyme(s) lead to dysfunction in the nervous system, eye, and other systems and ultimately lead to cell death and organspecific clinical manifestations. Most LSDs are inherited in an autosomal-recessive manner, 21 but some, like patients with neuronal ceroid lipofuscinosis 4B and nystagmus 18,22 and the case presented here, present autosomal-dominant inheritance. 23,24 Mutations in MANBA have been previously linked to β-mannosidosis (OMIM 248510), an autosomal-recessive LSD resulting in demyelination of the CNS.…”

Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease)

“…It is already known that contrary to the childhood forms, which are essentially all recessive disorders, the adult forms can have either recessive or dominant inheritance. 6,32,33 While it is now possible to survey the whole exome (or genome) for genetic variation with high-throughput sequencing technology, determining which of the many thousand variants identified are pathogenic remains challenging. However, this is still a good option for treating clinicians and may avoid the need for brain biopsy should a plausible variant be found in one of the known ANCL genes or in a gene known to cause an alternative late-onset neurologic disease.…”