Albinism or congenital nystagmus

Gene: MLPH

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (over 10 unrelated cases and functional evidence) for the association of this gene with Griscelli syndrome, type 3 (MIM #609227). Hence, this gene can be promoted to green rating on this panel in the next GMS update.

Created: 23 Apr 2026, 6:25 p.m. | Last Modified: 23 Apr 2026, 6:25 p.m.

Panel Version: 4.5

There are over 10 unrelated families reported with five different biallelic variants across 8 different publications. They presented with phenotype encompassing isolated oculocutaneous hypopigmentation (silvery-grey hair, eyebrows, eyelashes), skin hypomelanosis and irregular large melanin clumps in hair shafts. No neurological or immunological involvement was reported in them. There is also functional evidence available in support of the association.

This gene has been associated with Griscelli syndrome, type 3 in OMIM (MIM #609227) and the OMIM record was last accessed 23 April 2026. There is also definitive association for this gene on the Skin panel of Gene2Phenotype database.

Created: 23 Apr 2026, 6:24 p.m. | Last Modified: 23 Apr 2026, 6:24 p.m.

Panel Version: 4.2

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Griscelli syndrome, type 3, OMIM:609227; Griscelli syndrome type 3, MONDO:0012220

Publications

• 12897212
• 21883982
• 22711375
• 26337734
• 30389201
• 31721180
• 35602484

I don't know

Limited evidence for an association with hypopigmentation. Comments from OMIM: Griscelli syndrome is a rare autosomal recessive disorder that results in pigmentary dilution of the skin and the hair (silver hair), the presence of large clumps of pigment in hair shafts, and an accumulation of melanosomes in melanocytes. OMIM describes 2 patients with hypopigmentation without any immunologicic or neurologic manifestations; they were reported by Sanal et al. 2002 (PMID 12148598). Menasche et al. 2003 (PMID 12897212) identified a homozygous mutation in the MLPH gene in one of these patients and a homozygous deletion of the F-exon of the MYO5A gene. Comments from HGMDpro: Only 7 variants in total; 4 of these have Griscelli syndrome as the reported phenotype (2 missense variants, one nonsense and one frameshift variant). The misense variant reported by Menasche et al 2003 is present.

Created: 20 Mar 2019, 4:11 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Griscelli syndrome, type 3 609227 AR