Familial Autonomic Ganglionopathy Caused by Rare CHRNA3 Genetic Variants.

ABSTRACT:

Objective

To determine the molecular basis of a new monogenetic recessive disorder that results in familial autonomic ganglionopathy with diffuse autonomic failure.

Methods

Two adult siblings from one family (I-4 and I-5) and another participant from a second family (II-3) presented with severe neurogenic orthostatic hypotension (nOH), small nonreactive pupils, and constipation. All 3 affected members had low norepinephrine levels and diffuse panautonomic failure.

Results

Whole exome sequencing of DNA from I-4 and I-5 showed compound heterozygosity for c.907_908delCT (p.L303Dfs*115)/c.688 G>A (p.D230N) pathologic variants in the acetylcholine receptor, neuronal nicotinic, α3 subunit gene (CHRNA3). II-3 from the second family was homozygous for the same frameshi

SUBMITTER: Shibao CA 

PROVIDER: S-EPMC8279568 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature