/
DHX38 Gene Curation

DHX38 Gene Curation

Owned by Grant Fischer (Deactivated)
2024-12-13
3 min read

Gene-disease assertions not curated here (add link or write note):

Disease

Retinitis pigmentosa 84

Disease

Retinitis pigmentosa 84

Inheritance

Autosomal recessive

Prevalence

Orphanet

Medline Plus Genetics

Cumulative retinitis pigmentosa prevalence: 1-5/10,000

Source: Orphanet

Rapid or full curation?

Rapid
Full

ClinGen / GenCC / BabySeq / HGMD / OMIM

ClinGen - none, GenCC - strong by Invitae, BabySeq - none. HGMD with 2 reported variants described below.

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

1 proband from family with 4 affected sibs with G332D missense variant so rest used for segregation evidence below (PMID: 24737827): 0.1 point

2 probands from 2 families with R324Q missense variant with rest of families used for segregation evidence below (PMID: 30208423): 0.2 points

Segregation Evidence:

3 affected segs and 2 unaffected segs for family with G332D missense variant (PMID: 24737827): 1 point

8 affected segs and 4 unaffected segs for family with R324Q missense variant (PMID: 30208423): 3 points

Case/Control Evidence:

The G332D variant was not identified in any of 180 ethnically matched control individuals, nor in 7540 Africans or Caucasians and an in-house database that contained the exome data of 400 individuals (PMID: 24737827): 6 points

Experimental Evidence: N/A

Source: PMID: 24737827, 30208423

Clinical Validity Points Total

10.3 points

Source: PMID: 24737827, 30208423

Clinical Validity Classification

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

Moderate

Source: PMID: 24737827, 30208423

Molecular Mechanism

Loss of function

Gain of function

Dominant negative

Unknown

Other

Unknown; only missense variants described in HGMD

 

Penetrance

Complete (100%)

High (≥80%)

Moderate  (<80% and >20%)

Low (≤20%)

(list source/PMID)

Complete based on reported studies

Source: PMID: 24737827, 30208423

Age of Onset

Congenital

Pediatric

Adolescent

Adulthood

Late adulthood

(list source/PMID)

Pediatric based on reported studies

 

PMID: 24737827, 30208423

 

 

Severity

Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete.
Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high.
Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced.
Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low.
None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers.

Moderate - significant clinical morbidity but patients survive into adulthood

 

PMID: 24737827, 30208423

Clinical Features

autosomal recessive, early-onset form of retinitis pigmentosa, with onset of night blindness between ages 3 and 4 years and complete blindness as early as age 7

Sources: PMID: 24737827, 30208423

HPO Terms

https://hpo.jax.org/app/

Visual impairment

Gene SOPs & Notes

 LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant

Curation Summary

- The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Variable expression or severity:
The severity and expressivity of the disorder is highly variable, even within families.
- If multiple conditions associated with the gene:
It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs).

- Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dIsease relationship is limited

The DHX38 is moderately associated with autosomal recessive retinitis pigmentosa 84, which is characterized by early-onset form of retinitis pigmentosa, with onset of night blindness between ages 3 and 4 years and complete blindness as early as age 7 (PMIDs: 24737827, 30208423).

Case ID, Curator name, Date, Jira ticket link

Grant Fischer - 12/13/2024

 

 

Related content