Aortopathy_Connective Tissue Disorders

Gene: ALDH18A1

Green List (high evidence)

PMID: 30071989; not a HTAAD gene by clingen working group

Cutis laxa, autosomal dominant 3 (MIM# 616603)

PMID: 28228640;
- Born to consanguineous parents and harbour a de novo missense p.(Arg126His). no functional done

PMID: 26320891;
- 8 unrelated individuals born to non-consanguineous families clinically diagnosed with de-barsy syndrome (DBS) or wrinkly skin syndrome. All variants occur at codon Arg138 and parental DNA from 6 probands confirmed de novo origin. (NOTE: table 1 states paternal origin however this is referring to the allele not variant (Figure S1)).
- Imaging of patients's cells showed increased accumulation of mutant protein at the mitochondrial outer membrane.
- Biochemical studies using patients' fibroblasts demonstrated LoF


Cutis laxa, autosomal recessive, type IIIA (MIM# 219150)

PMID: 24913064;
- 2 patients from consanguineous families, 1x fs (c.2131del)+ 1x 1522bp del (resulting in exon 15 del)
- clinical features like facial dysmorphism, hypotonia, adducted thumbs and cutis laxa, which are frequently found in progeroid cutis laxa syndromes. In addition, they had cardiovascular abnormalities

PMID: 18478038;
- missense c.2350C>T; p.(His784Tyr) found in a a consanguineous New Zealand Maori family with 4 affecteds.
- patients' fibroblasts showed no defect in Proline accumulation

PMID: 21739576;
This severely affected child, born to consanguineous parents of Pakistani origin, presented with lax, wrinkled and thin skin with dilated and tortuous subcutaneous blood vessels, corneal clouding, and hypotonia. The child had severe global developmental delay and feeding difficulties and died in infancy for an unknown reason. The proband was homozygous for a mutation in ALDH18A1 , c.1923 + 1G > A

PMID: 22411858;
pair of siblings chet for p.(Ser742Ile) and p.(Arg425Cys)
Sources: Literature

Created: 1 Jul 2020, 2:55 a.m.

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Cutis laxa, autosomal dominant 3 (MIM# 616603); Cutis laxa, autosomal recessive, type IIIA (MIM# 219150)

Publications

• PMID: 30071989
• 26320891
• 24913064
• 18478038
• 21739576
• 22411858
• 28228640