Hereditary neuropathy or pain disorder

Gene: LAS1L

I don't know

Comment on list classification: There are two unrelated cases and some functional evidence reported in support of the association of LAS1L gene with SMARD-like phenotype. Karen Stals reported in her review that there is an additional case in Exeter, but the variant is of uncertain significance. Hence, this gene should be rated amber with the current evidence.

However, 'watchlist' tag added so that this gene will be reviewed in light of new evidence.

Created: 27 Jul 2026, 2:52 p.m. | Last Modified: 27 Jul 2026, 3:15 p.m.

Panel Version: 8.21

LAS1L is associated with Wilson-Turner syndrome, which is a syndromic intellectual developmental disorder in OMIM (MIM #309585, last accessed 26 July 2026).

PMID:24647030 (2014) reported the identification of a de novo hemizygous missense variant (c.1430G>A, p.Ser477Asn) in a male neonate proband with fatal congenital spinal muscular atrophy with respiratory distress (SMARD)-like motor neuron disease. There is supporting evidence available from zebrafish rescue experiments.

PMID:35627110 (2022) reported the identification of a novel hemizygous synonymous variant in the LAS1L gene inherited from an unaffected mother (c.846G>C, p.Thr282=) in an eighteen-month old male patient with a SMARD phenotype. Maternal fibroblasts showed no coding-region transcript, suggesting skewed X-inactivation silencing the variant allele in her cells.

Created: 27 Jul 2026, 2:46 p.m. | Last Modified: 27 Jul 2026, 2:54 p.m.

Panel Version: 8.21

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Wilson-Turner syndrome, OMIM:309585; Spinal muscular atrophy with respiratory distress (SMARD)-like motor neuron disease

Publications

• 24647030
• 35627110

I don't know

2 publications report SMARD-like phenotypes in 2 affected individuals with hypotonia, respiratory distress and muscle weakness. Additional case in Exeter - reported as variant of uncertain significance - suggest amber rating

Created: 11 Jun 2026, 11:26 a.m. | Last Modified: 11 Jun 2026, 11:26 a.m.

Panel Version: 8.4

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
SMARD-like, respiratory distress, apnoea, hypotonia

Publications

• PMID: 35627110
• PMID: 24647030

I don't know

Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 29 Apr 2019, 12:53 p.m.

Red List (low evidence)

More evidence needed. PMID: 24647030 - de novo mutation in the X-linked LAS1L gene (is absent from gnomAD). knockdown of las1l in zebrafish results in dysmorphic embryos with early lethality

Created: 29 Apr 2019, 12:30 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Publications

• 24647030

Red List (low evidence)

Single case but de novo mutation

Created: 9 Dec 2015, 8:50 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Red List (low evidence)

Single case but de novo mutation

Created: 8 Dec 2015, 3:07 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)