Ehlers Danlos syndrome with a likely monogenic cause

Gene: ATP6V1E1

Green List (high evidence)

Comment on list classification: There are 3 unrelated individuals reported in literature with biallelic ATP6V1E1 variants and syndromic cutis laxa, with variable features including congenital heart defects, hypotonia, aortic dilation, contractures, and more. Hence, this gene can be promoted to Green on Ehlers Danlos syndrome with a likely monogenic cause.

Created: 9 Sep 2026, 1:35 p.m. | Last Modified: 9 Sep 2026, 1:35 p.m.

Panel Version: 4.20

PMID: 27023906 Alazami et al., 2016
Study of a cohort of 40 families with inherited connective tissue disorders.
Family 5 - Saudi brothers homozygous for ATP6V1E1:c.634C>T, p.Arg212Trp (2 alleles reported in gnomAD v4.1.1., no hom). Seq method: WES followed by WGS (ATP6V1E1 variant missed by WES due to poor coverage).
The sibs presented with cutis laxa, dysmorphic facial features, strabismus, congenital heart defects, nephrocalcinosis, midline cleft palate. Pregnancy was complicated by oligohydramnios and hydronephrosis. Parents are first cousins, unaffected.

PMID: 28065471 Van Damme et al., 2018
Report of 5 families with syndromic cutis laxa and biallelic variants in ATP6V1E1 (2 families from Iran and Kuwait) and ATP6V1A (3 families from Germany, Turkey, and Pakistan).
Both families with ATP6V1E1 variants were consanguineous, and the probands were homozygous for a ATP6V1E1 variant each: c.383T>C, p.Leu128Pro in PI & c.634C>T, p.Arg212Trp in PII.
Variant p.Leu128Pro not found in gnomAD v4.1.1.
Patient phenotypes: cutis laxa 2/2, severe hypotonia 1 (1 not determined), cardiac abnormalities 2/2, aortic dilation 1/2, contractures 1/2; seizures and MRI abnormalities were not determined.
All parents reported to be unaffected.

This gene is associated with Cutis laxa, autosomal recessive, type IIC, OMIM:617402 in OMIM, and ATP6V1E1-related cutis laxa (biallelic_autosomal) in G2P with a Strong confidence level (resources accessed 9th Sept 2026).
Sources: Literature

Created: 9 Sep 2026, 1:31 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cutis laxa, autosomal recessive, type IIC, OMIM:617402; autosomal recessive cutis laxa type 2C, MONDO:0027462

Publications

• 27023906
• 28065471