Albinism or congenital nystagmus

Gene: BLOC1S6

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 3 Mar 2022, 4:42 p.m. | Last Modified: 3 Mar 2022, 4:42 p.m.

Panel Version: 1.22

Comment on list classification: Changed rating to Amber so that Green genes on this panel reflect the NHS signed-off version. This will be reviewed at the next GMS panel update.

Created: 19 Oct 2020, 11:32 a.m. | Last Modified: 19 Oct 2020, 11:32 a.m.

Panel Version: 1.6

Comment on list classification: Promoting from amber to red, as there are now 3 cases reported.

Created: 21 May 2020, 3:39 p.m. | Last Modified: 21 May 2020, 3:39 p.m.

Panel Version: 1.5

Provisionally associated with ?Hermansky-pudlak syndrome 9 #614171 (AR) in OMIM.
BLOC1S6 is also known as PLDN and HPS9.

PMID: 32245340 - Michaud et al 2020 - report 1 patient presenting with ocular features of albinism. Genetic analysis revealed two compound heterozygous variants in the BLOC1S6 gene. (Abstract only accessed).

PMID: 22461475 - Badolato et al 2012 - report a northern Italian girl with oculocutaneous albinism, nystagmus, and normal neurologic development who presented with recurrent cutaneous infections but without hemorrhagic episodes. She had thrombocytopenia and leukopenia, with normal platelet aggregation. WES found a homozygous nonsense mutation, c.232C > T (p.Q78X) in PLDN (BLOC1S6). This variant was confirmed homozygous in the patient and heterozygous in her parents by Sanger sequencing, and was associated with absent PLDN protein expression

PMID: 26575419 - Yousaf et al 2016 - report a Pakistani family in which the proband had a nonsense mutation is the HPS9/PLDN gene (c.232C>T, p.Gln78*). The 4-year-old female patient reported had Oculocutaneous albinism, photophobia, nystagmus, prolonged bleeding and clotting times, which indicate platelet dysfunction.

PMID: 21665000 - Cullinane et al 2011 - RETRACTED PAPER - report 1 9-month old male patient of Indian ancestry with a homozygous c.232C>T; p.Gln78Och mutation and HPS-like phenotype. This paper has been retracted due to falsified and/or fabricated gel images which represent expression of PLDN in fibroblasts and melanocytes.

Summary: 3 reports of patients with oculocutaneous albinism + retracted paper.

Created: 21 May 2020, 3:38 p.m. | Last Modified: 21 May 2020, 3:38 p.m.

Panel Version: 1.4

I don't know

Limited evidence available. Comments from OMIM: Only one patient is recorded. Comments from HGMDpro: Only 2 variants in total (nonsense and frameshift); both of these has Hermansky-Pudlak syndrome as the reported phenotype; two different authors

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

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Hermansky-pudlak syndrome 9 614171 AR