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Primary immunodeficiency

Gene: BLOC1S6

Amber List (moderate evidence)

BLOC1S6 (biogenesis of lysosomal organelles complex 1 subunit 6)
EnsemblGeneIds (GRCh38): ENSG00000104164
EnsemblGeneIds (GRCh37): ENSG00000104164
OMIM: 604310, Gene2Phenotype
BLOC1S6 is in 10 panels

4 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Promoting from red to amber. The immune dysfunction phenotype is not as clear as the platelet anomalies and ocular / oculocutaneous albinism phenotype. Therefore rating this gene as amber for now.
Created: 21 May 2020, 3:20 p.m. | Last Modified: 21 May 2020, 3:20 p.m.
Panel Version: 2.173
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. Extended hematological studies confirmed the platelet storage pool disease with absence of dense granules and abnormal platelet aggregation. (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 here, 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 This paper has been retracted due to falsified and/or fabricated gel images which represent expression of PLDN in fibroblasts and melanocytes.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 + retracted paper. 2 out of the 3 patients had abnormal platelet aggregation. The 3rd had thrombocytopenia and leukopenia, with normal platelet aggregation.
Created: 22 Apr 2020, 4:34 p.m. | Last Modified: 22 Apr 2020, 4:54 p.m.
Panel Version: 2.124

Publications

Zornitza Stark (Australian Genomics)

I don't know

A new report of affected individual with pigmentary and platelet abnormalities, and compound heterozygous variants in this gene. Borderline Red/Amber.
Created: 9 Apr 2020, 1:44 a.m. | Last Modified: 9 Apr 2020, 1:44 a.m.
Panel Version: 2.46

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Hermansky-Pudlak syndrome 9, MIM# 614171

Publications

Sophie Hambleton (Newcastle University)

Red List (low evidence)

Only 1 reported patient (a previous report had to be retracted).
Created: 19 Jun 2018, 5:47 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Louise Daugherty (Genomics England Curator)

I don't know

?Hermansky-Pudlak: one patient - amber, relevant phenotype
Created: 26 Sep 2019, 3:50 p.m. | Last Modified: 26 Sep 2019, 3:50 p.m.
Panel Version: 1.130
Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is only enough evidence to rate this gene Red
Created: 26 Sep 2019, 2:50 p.m. | Last Modified: 26 Sep 2019, 2:50 p.m.
Panel Version: 1.127
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is only enough evidence to rate this gene Red


Genes with discrepant ratings (PID 100K vs sumbmitted LNGLH submitted Immunology lists)--agreed rating in webex call 28 March 2019
Created: 26 Sep 2019, 2:50 p.m. | Last Modified: 26 Sep 2019, 2:52 p.m.
Panel Version: 1.127
Comment on list classification: Changed from Amber to Red after external clinical review, only one bonafide case
Created: 20 Jun 2018, 3:10 p.m.
After review decided to keep as Amber- currently there is only one case for HPS9 need more individuals to determine if immunodeficiency is a feature of BLOC-1 deficiency
Created: 11 May 2018, 4:31 p.m.
Comment on publications: one one affected reported to date (2012). Added HPS gene review PMID: 20301464 (2017)
Created: 11 May 2018, 4:25 p.m.
Comment on phenotypes: added PID phenotype
Created: 11 May 2018, 4:24 p.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.
Created: 20 Apr 2018, 12:25 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: BLOC1S6, GRID_Gene_Symbol: BLOC1S6, GRID_Transcript_ENS_Community submitted: ENST00000220531, GRID_Transcript_RefSeq: NM_012388.3, GRID_Transcript_ENS_used_on_Production: ENST00000220531
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Victorian Clinical Genetics Services, London North GLH
  • NHS GMS
  • GRID V2.0
  • GRID V2.0North West GLH
Phenotypes
  • Hermansky-pudlak syndrome 9, 614171
  • HPS9, palladin deficiency (NK cell defect)
  • Immune Dysregulation
Tags
for-review
OMIM
604310
Clinvar variants
Variants in BLOC1S6
Penetrance
None
Publications
Panels with this gene

History Filter Activity

21 May 2020, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: BLOC1S6.

21 May 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: bloc1s6 has been classified as Amber List (Moderate Evidence).

22 Apr 2020, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: BLOC1S6 were set to 22461475,20301464,26575419

26 Sep 2019, Gel status: 1

Added New Source, Added New Source, Added New Source, Added New Source, Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Red was added to BLOC1S6. Source GRID V2.0North West GLH was added to BLOC1S6. Source GRID V2.0 was added to BLOC1S6. Source NHS GMS was added to BLOC1S6. Source Victorian Clinical Genetics Services, London North GLH was added to BLOC1S6. Rating Changed from No List (delete) to Red List (low evidence)

26 Sep 2019, Gel status: 0

Clear Sources

Louise Daugherty (Genomics England Curator)

All sources for gene: BLOC1S6 were removed

26 Sep 2019, Gel status: 1

Added New Source, Added New Source, Added New Source

Louise Daugherty (Genomics England Curator)

Source GRID V2.0 was added to BLOC1S6. Source Expert Review Red was added to BLOC1S6. Source Victorian Clinical Genetics Services, London North GLH, NHS GMS was added to BLOC1S6.

24 Sep 2019, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene: BLOC1S6 were set to

18 Sep 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to BLOC1S6.

17 Sep 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Louise Daugherty (Genomics England Curator)

gene: BLOC1S6 was added gene: BLOC1S6 was added to Primary immunodeficiency. Sources: Other Mode of inheritance for gene: BLOC1S6 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: BLOC1S6 were set to Hermansky-pudlak syndrome 9, 614171; HPS9, palladin deficiency (NK cell defect); Immune Dysregulation Review for gene: BLOC1S6 was set to RED