Amyotrophic lateral sclerosis/motor neuron disease

Gene: NEFH

I don't know

the C-terminal region of the NEFH gene contains a functional domain with 43 or 44 repeat motifs of the amino acids Lys—Ser-Pro, named S (short) and L (long) allele respectively.
7849698 describes an two deletions in the C-terminal region, in 5 sporadic als patients.
9931323 found 4 deletions in the C-terminal region in 4 als patients, 3 unaffected individuals and in 2 controls. 14722583 found an association between the S allele and ALS in a Russia population.
Hence, reduced penetrace for the deletions within the repeat C- terminal region.
As they are in the context of a repeat, I am not sure WGS would pick them up

Created: 18 Dec 2016, 9:20 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

I don't know

Comment when marking as ready: Pathogenicity remains uncertain

Created: 19 Dec 2016, 3:37 p.m.

Deletions in the heavy neurofilament subunit (NFH) tail have been identified in nine families. Not fully penetrant. May just confer susceptibility. Not recognised on Orphanet or G2P

Created: 24 Nov 2016, 2:29 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amyotrophic lateral sclerosis, susceptibility to 105400

Publications

• 7849698,9931323

Comment on list classification: Appears to be a susceptibility gene/disease-modifying gene - unsure whether this should be green despite being on the NHNN ALS/MND NGS panel.

Created: 15 Jun 2016, 2:19 p.m.

This gene is on the ALS/MND NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual: "NEFH encodes the heavy neurofilament protein. This protein is commonly used as a biomarker of neuronal damage and susceptibility to amyotrophic lateral sclerosis (ALS) has been associated with mutations in this gene."

Created: 13 Jun 2016, 9:13 a.m.