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Hearing loss

Gene: CISD2

Amber List (moderate evidence)

CISD2 (CDGSH iron sulfur domain 2)
EnsemblGeneIds (GRCh38): ENSG00000145354
EnsemblGeneIds (GRCh37): ENSG00000145354
OMIM: 611507, Gene2Phenotype
CISD2 is in 15 panels

3 reviews

Eleanor Williams (Genomics England Curator)

I don't know

Comment on list classification: Promoting this gene from red to amber as several cases reported with hearing loss as a feature, but not as the first presenting feature.
Created: 8 Sep 2020, 3:58 p.m. | Last Modified: 8 Sep 2020, 3:58 p.m.
Panel Version: 2.52
Associated with Wolfram syndrome 2 #604928 (AR) in OMIM and Gene2Phenotype (Eye and Developmental disorders panel).

Summary: 3 independent cases of variants in CISD2 are reported in families with Wolfram syndrome 2. Hearing loss is a feature, but it seems that diabetes mellitus and ulcers are the predominant first presenting feature.

PMID: 10739754 - El Shanti et al 2000 - first reports of four consanguineous Jordanian families (16 individuals) with individuals presenting with Wolfram sydrome clinical features. Diabetes mellitus was reported in 3/4 families 13 indviduals), hearing loss in all families (14 individuals) and optic-nerve atrophy in all individuals. Urinary-tract dilatation was present in 8/16 individuals and peptic ulcers in 11/16. The candidate region was mapped to 4q22-24.

PMID: 17846994 - Amr et al 2007 - investigate the patients described in 3 of the families in El Shanti et al further - the same homozygous missense variant in ZCD2 (CISD2) was found in all 3 families. They also screened 377 hearing loss probands for mutations in ZCD2. No mutations were identified in this cohort.

PMID: 25056293 - Mozzillo et al 2104 - report a Caucasian 17 year old girl with diabetes mellitus, optic neuropathy, intestinal ulcers, sensorineural hearing loss, and defective platelet aggregation to ADP. Bleeding upper intestinal ulcers were the first reported symptom. A novel homozygous deletion covering exon2 of CISD2 was found in the proband. Her brother and parents carried the heterozygous mutation and were apparently healthy, although they showed subclinical defective platelet aggregation.

PMID: 25371195 - Rondinelli et al 2015 - report an Italian family with 2 affected sisters. First presentation of Wolfram syndrome 2 was anaemia and severe duodenal ulcers in their first months of life. Both sisters were diagnosed with non-autoimmune insulin-requiring diabetes mellitus at the age of 12, Hearing loss was mild and limited to high frequencies and was detected in both patients when they were 13 and 10 years old, respectively. Both probands had a homozygous substitution in the donor splice site of intron 1 of CISD2.
Created: 8 Sep 2020, 3:55 p.m. | Last Modified: 8 Sep 2020, 3:55 p.m.
Panel Version: 2.49

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Wolfram syndrome 2 #604928

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

SNHL is a feature of this condition. The relative timing of symptom onset (DM, optic atrophy vs SNHL) appears variable, with at least one family reported where SNHL was the initial feature. Consider including as Green on this panel.
Created: 29 Jan 2020, 12:10 a.m. | Last Modified: 29 Jan 2020, 12:10 a.m.
Panel Version: 2.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Wolfram syndrome 2, MIM# 604928

Publications

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

Jun Shen (Harvard Medical School)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#604928:Wolfram syndrome 2[Sensorineural hearing loss, high frequency; Optic atrophy (may be asymptomatic in some patients)Optic neuropathy; Peptic ulcer disease (in some patients); Urinary tract dilatation (in some patients)Impaired renal function (in some patients); Depression (in some patients); Diabetes mellitus; Bleeding associated with peptic ulcer diseaseDefective platelet aggregation in response to ADP]

Publications

History Filter Activity

8 Sep 2020, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag for-review tag was added to gene: CISD2.

8 Sep 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: cisd2 has been classified as Amber List (Moderate Evidence).

8 Sep 2020, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: CISD2 were changed from hearing loss to hearing loss; Wolfram syndrome 2 604928

8 Sep 2020, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: CISD2 were set to

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

CISD2 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Emory Genetics Laboratory