Hereditary neuropathy or pain disorder

Gene: CTDP1

Green List (high evidence)

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

Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.

Panel Version: 6.148

The founder intronic CTDP1 variant is associated with Congenital cataracts, facial dysmorphism, and neuropathy (OMIM:604168). This widely reported variant: NM_004715.5(CTDP1):c.863+389C>T is situated deep within intron 6 of CTDP1 and requires specific testing to be detected (PMID: 14517542; 15322984; 16194727; 23408394; 24690360; 29174527; 20301787)

Created: 4 Nov 2024, 11:26 a.m. | Last Modified: 4 Nov 2024, 11:26 a.m.

Panel Version: 6.20

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital cataracts, facial dysmorphism, and neuropathy, OMIM:604168; congenital cataracts-facial dysmorphism-neuropathy syndrome, MONDO:0011402

Publications

• 15322984
• 20301787
• 10439962
• 29174527
• 14517542
• 16194727
• 24690360
• 21824574
• 23408394

Green List (high evidence)

As per Natalie Forrester review. PN estabished part of CTDP1 phenotype. Common in Roma populations but mostly due to an intronic variant that would need ot be included

Created: 20 Oct 2024, 9:26 a.m. | Last Modified: 20 Oct 2024, 9:26 a.m.

Panel Version: 5.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
cataratcs; facial dysmorphism; peripheral neuropathy

Publications

• 10439962: 29174527: 21824574

I don't know

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype (dysmorphic, cataract) - founder mutation in Roma populations, intronic

Created: 6 Dec 2019, 3:36 p.m. | Last Modified: 6 Dec 2019, 3:36 p.m.

Panel Version: 0.44

Comment on list classification: This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.

Created: 6 Dec 2019, 3:35 p.m. | Last Modified: 6 Dec 2019, 3:35 p.m.

Panel Version: 0.44

Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 29 Apr 2019, 12:53 p.m.

Green List (high evidence)

Well characterised founder intronic mutation. Bristol currently don't cover this intronic region on our NGS panel but have Sanger primers designed to target it, using these we have identified one homozygous patient who had congenital demyelinating neuropathy. PMID:24690360 - 10 CCFDN children living in the Czech Republic. All patients are children of different ages, all of Gypsy origin born in the Czech Republic. Molecular genetic testing for the founder CTDP1 gene mutation was performed. All patients are homozygous for the c.863 + 389C>T mutation in the CTDP1 gene; PMID:16194727 - Demonstrated the presence of the homozygous IVS6+389C>T mutation in the CTDP1 gene in a family with congenital cataracts facial dysmorphism neuropathy. PMID: 14517542 - original report of this variant in an endogamous group of Vlax Roma.

Created: 29 Apr 2019, 12:30 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital cataract, facial dysmorphism and demyelinating neuropathy (CCFDN)

Publications

• 24690360
• 16194727
• 14517542

Variants in this GENE are reported as part of current diagnostic practice

Comment on list classification: Multiple publications showing a founder variant to be associated with Congenital cataract, facial dysmorphism and demyelinating neuropathy (CCFDN) in Roma populations. As this is a single founder variant, this gene should be red as examining loss-of-function variants would not be suitable.

Created: 10 May 2016, 1:41 p.m.

Green List (high evidence)

only 1 recessive intronic roma founder mutation known

Created: 9 Dec 2015, 4:47 p.m.

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Complex phenotype

Created: 8 Dec 2015, 3:05 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown