Hereditary neuropathy or pain disorder

Gene: DRP2

This gene currently has no phenotype listed in OMIM and so checked PMID:26227883 to make sure the same gene name is listed. Its is, so added the gene-checked tag.

Created: 16 Oct 2023, 5:05 p.m. | Last Modified: 16 Oct 2023, 5:05 p.m.

Panel Version: 3.60

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, biallelic mutations in females following NHS Genomic Medicine Service approval.

Created: 10 Oct 2023, 6:06 p.m. | Last Modified: 10 Oct 2023, 6:06 p.m.

Panel Version: 3.58

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Green List (high evidence)

Comment on list classification: As reviewed by Zornitza Stark (Australian Genomics), there is sufficient evidence (3 unrelated cases and functional studies) for this gene to be promoted to GREEN at the next major review.

Created: 26 Apr 2023, 1:57 p.m. | Last Modified: 26 Apr 2023, 1:57 p.m.

Panel Version: 3.15

PMID:26227883 reported a 60-year-old man presenting with length dependent sensorimotor neuropathy and was identified with a hemizygous nonsense variant (c.805C>T/ p.Q269X) in DRP2 gene. Similarly, PMID:29473052 reported a 42-year-old man with early adult-onset sensorimotor neuropathy and identified with a hemizygous nonsense variant (c.1039C>T/ p.Q347X). His unaffected mother is a carrier for the variant.

PMID:31217940 reported hemizygous deletion variant in DRP2 gene in two Iranian brothers (22 and 16 years of age) presenting with neuropathy and they inherited this variant from their carrier mother.

This gene has not yet been reported with relevant phenotypes either in OMIM or in Gene2Phenotype.

Created: 26 Apr 2023, 1:55 p.m. | Last Modified: 26 Apr 2023, 1:55 p.m.

Panel Version: 3.13

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Publications

• 22764250
• 26227883
• 29473052
• 31217940

Green List (high evidence)

Three unrelated families and functional data.

Created: 31 Mar 2020, 9:05 a.m. | Last Modified: 31 Mar 2020, 9:05 a.m.

Panel Version: 1.4

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
X-linked Charcot-Marie-Tooth

Publications

• 26227883
• 11430802
• 31217940
• 22764250
• 29473052

I don't know

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). New evidence/re-evaluation of evidence - promotion to Green? 2 cases but functional studies don't show features of neuropathy - Amber? More evidence needed

Created: 6 Dec 2019, 2:29 p.m. | Last Modified: 6 Dec 2019, 2:29 p.m.

Panel Version: 0.36

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, 1:19 p.m. | Last Modified: 6 Dec 2019, 1:19 p.m.

Panel Version: 0.11

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.

I don't know

Now second family with a nonsense mutation. PMID: 29473052 - c.1039C>T, p.Q347X mutation was found in a patient with sensorimotor neuropathy (unaffected mother carrier - X linked). 1 allele in gnomAD. PMID: 26227883 - Drp2 knockout mice lack Cajal bands and display myelin abnormalities but do not develop weakness or abnormal nerve conductions. Another Q269X variant in a 3 generation family, some with CMT and others just with hammertoes and abnormal gait

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

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Publications

• 29473052
• 26227883

Green List (high evidence)

2 families with functional evidence

Created: 16 May 2019, 3:03 p.m.

Single family

Created: 9 Dec 2015, 8:50 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Red List (low evidence)

Single family

Created: 8 Dec 2015, 3:07 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females