Clefting

Gene: LRRC32

Green List (high evidence)

Comment on list classification: There are now 3 unrelated individuals with 3 different homozygous LRRC32 variants and clefting. Hence, this gene should be promoted to Green at the next update.

Created: 10 Apr 2026, 9:46 a.m. | Last Modified: 10 Apr 2026, 9:46 a.m.

Panel Version: 6.25

PMID: 40721351 Shboul et al., 2025
Patient 4 - female fetus, Jordanian ancestry, parents first degree consanguineous; homozygous for LRRC32:c.1630C>T, p.Arg544* mutation; presented with growth delay at 18 weeks gestation; fetal growth retardation, oligohydramnios in addition to both lateral ventricle dilatation and right renal pelvis dilation with ventricular septal defect. At 28 weeks GA, the fetus was terminated - normal female with no external gross anomalies detected. Same variant as in PMID: 30976112 (2 Palestinian families).

https://doi.org/10.1016/j.rare.2025.100101 Kumari et al., 2025
Report of a male proband, Pakistani origin, consanguineous parents. He was homozygous for a stop-gain variant in LRRC32 c.1261C>T (p.Arg421*) - confirmed in trans. Variant is rare in gnomAD v4 (MAF = 0.00004464), no homozygotes. Patient presented with cleft palate, proliferative retinopathy (corneal clouding, congenital blindness), and global developmental delay. He also had extremely dry, scaly skin.

Created: 10 Apr 2026, 9:42 a.m. | Last Modified: 10 Apr 2026, 9:48 a.m.

Panel Version: 6.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074

Publications

• 40721351
• https://doi.org/10.1016/j.rare.2025.100101

I don't know

PMID:30976112 reported two unrelated families with global developmental delay, cleft palate, and proliferative retinopathy and they were identified with the same homozygous LRRC32 variant c.1630C>T/ p.Arg544Ter. This variant was suggested to be founder variant, as indicated by haplotype analysis.

PMID:35656379 reported a different homozygous LRRC32 variant (c.1354 G > A/ p.Glu452Lys) in a 15-year-old male with cleft palate, prenatal and postnatal severe growth retardation, global developmental delay, dysmorphic facial features and progressive vitreoretinopathy.

This gene has already been associated with relevant phenotypes in OMIM (MIM #619074), but not yet in Gene2Phenotype.
Sources: Literature

Created: 20 Feb 2024, 4:16 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cleft palate, proliferative retinopathy, and developmental delay, OMIM:619074

Publications

• 30976112
• 35656379