Early onset dystonia

Gene: GCDH

Green List (high evidence)

Marti-Masso, et al. (2012, PMID: 21912879) presented a family with early-onset generalized dystonia from Spain. Whole-exome-sequencing revealed homozygous GCDH c.1275G>A (p.Val400Met) variant in 55 years of age affected female (age of dystonia onset at infancy). Sanger sequencing of the GCDH gene revealed the same variant in 50 years of age affected sister (whose clinical evolution was similar to the one seen in her sibling) in the homozygous state; and in healthy parents in the heterozygous state. This variant was absent from a control group of ethnically matched 184 chromosomes. The 3-hydroxy glutaric acid in urine was increased in both siblings.

- Please note that GCDH c.1275G>A (p.Val400Met) variant was present in gnomAD v2.1.1 with maximum minor allele frequency (MAX MAF) of 0.01627% (21/129070; 0 homozygotes) in European (non-Finnish) population

Sitta, et al. (2021, PMID: 33064266) presented 24 unrelated glutaric aciduria type 1 cases from Brazil. Sequencing of GCDH revealed variants in homozygous or compound heterozygous state in 7 cases who experienced dystonia (age at diagnosis was at 26 years or earlier; consanguinity was present in 2 cases).

- Please note that variants found in these 7 cases were absent or sufficiently rare (MAX MAF of 0.03149% or lower) in gnomAD v2.1.1

Created: 8 Dec 2021, 1:32 p.m. | Last Modified: 8 Dec 2021, 1:32 p.m.

Panel Version: 1.99

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• PMID: 21912879
• 33064266