Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: SLC35C1

Green List (high evidence)

agree with green gene

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

YES- this is covered on our targeted exome

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

Green List (high evidence)

Green List (high evidence)

Comment on list classification: Rating this gene green since likely pathogenic variants found in 3 independant families

Created: 15 May 2018, 4:22 p.m.

SLC35C1 is associated with Congenital disorder of glycosylation type IIc (CDG2C) in OMIM. OMIM states it is also known as leukocyte adhesion deficiency II and is characterised by a lack of fucosylated glycoconjugates causing immunodeficiency and severe mental and growth retardation so this phenotype is relevant to the PID panel. Lühn et al., 2001 (PMID:11326279) identified a homozygous mutation (R147C) in the SLC35C1 gene from fibroblasts of a Turkish patient with CDG2C (R147C). This was confirmed by Lubke et al., 2001 (PMID: 11326280). Lubke et al., 2001 also identified another homozygous mutation (T308R) in the SLC35C1 gene in 2 additional patients with LAD2 from unrelated Arab families in Israel. These two substitutions are located in highly conserved transmembrane domains Etzioni et al. 2002 (PMID: 12116250) reported that the previously reported variants in Arab-Israeli families (Lubke et al., 2001, Etzioni et al., 1992 (PMID: 1279426 and Etzioni and Tonetti, 2000 (PMID: 11213799) were homozygous for the T308R mutation. All 3 patients lived in the same area, suggesting a founder mutation. Dauber et al. (2014) (PMID:24403049) report 2 British brothers with congenital disorder of glycosylation type IIc (CDG2C; 266265), Dauber et al. (2014) identified compound heterozygous mutations in the SLC35C1 gene: a E31X substitution, and a 3-bp deletion c.501_503delCTT resulting in the loss of a phenylalanine in the fifth transmembrane domain. The mutations segregated with the disorder in the family. Gene2Phenotype list 3 variants (one nonsense, two missense) in this gene associated with Congenital disorder of glycosylation. Rating this gene green since likely pathogenic variants found in 3 independant families (Lühn et al. 2001, Lubke et al., 2001/Etzioni et al. 2002 and Dauber et al. 2014).

Created: 15 May 2018, 4:22 p.m.

Comment on phenotypes: Added MIM number to Congenital disorder of glycosylation, type IIc

Created: 10 May 2018, 2:41 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 11326279
• 11326280
• 12116250
• 1279426
• 11213799
• 24403049

Green List (high evidence)

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 enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

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 enough evidence to rate this gene Green.

Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.

Panel Version: 1.94

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): SLC35C1 .PanelApp HGNC gene symbol check: SLC35C1 . IUIS Disease: Leukocyte adhesion deficiency type 2 (LAD2) . IUIS Inheritance: AR .T cells: Increased activated T cells, .B cells: N/A, .IUIS Other affected cells: N + M. IUIS Associated features: Mild LAD type 1 features with hh-blood group, growth retardation, developmental delay. IUIS Major category: Congenital defects of phagocyte number or function. IUIS Subcategory: Defects of Motility

Created: 2 Jul 2018, 10:35 a.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: 19 Apr 2018, 3:09 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: LAD2 / FUCT1, PanelApp HGNC gene symbol check: SLC35C1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Phagocytic disorders / Leukocyte adhesion deficiency (LAD) / Leukocyte adhesion deficiency (LAD)

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: SLC35C1, GRID_Gene_Symbol: SLC35C1, GRID_Transcript_ENS_Community submitted: ENST00000314134, GRID_Transcript_RefSeq: NM_018389.4, GRID_Transcript_ENS_used_on_Production: ENST00000314134

Created: 17 Apr 2018, 12:12 p.m.