Bleeding and Platelet Disorders

Gene: DIAPH1

Green List (high evidence)

OMIM:
Deafness, autosomal dominant 1, with or without thrombocytopenia (AD)
Seizures, cortical blindness, microcephaly syndrome (AR) - Microcephaly (up to -10 SD)

Microcephaly:
PMID: 24781755 (2015) - five individuals from a consanguineous family with severe microcephaly >2SD below the mean for age with homozygous nonsense variant in DIAPH1

PMID: 26463574 (2016) - two different homozygous LOF variants identified in two unrelated consanguineous families. The affected individuals were diagnosed with postnatal microcephaly (>2SD), early-onset epilepsy, severe vision impairment, and pulmonary symptoms including bronchiectasis and recurrent respiratory infections.

Summary (microcephaly) - Three unrelated consanguineous families with homozygous LOF variants

Deafness:
PMID: 24781755 (2016) - Two unrelated pedigrees with a heterozygous truncating (confirmed) variant in 4 and 3 individuals in each family with macrothrombocytopenia and sensorineural hearing loss. Gain of function is the suspected mechanism.

PMID: 27707755 (2016) - Heterozygous nonsense variant in two families with hearing loss.

PMID: 27808407 (2017) - Two families with different heterozygous truncating variants with ADNSHL. An association with thrombocytopenia was also identified.

PMID: 28003573 (2017) - Novel missense variant in a patient with ADNSHL.

PMID: 28815995 (2017) - Heterozygous nonsense variant in a family with progressive hearing loss and macrothrombocytopenia

Summary (deafness): at least eight families with AD deafness and in some cases macrothrombocytopenia

Created: 2 Sep 2020, 6:15 a.m. | Last Modified: 2 Sep 2020, 6:15 a.m.

Panel Version: 0.4114

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Deafness; thrombocytopenia; Seizures; cortical blindness; microcephaly

Publications

• PMID: 24781755
• 26463574
• 24781755
• 27808407
• 28003573
• 28815995

Green List (high evidence)

At least four unrelated families reported.
Sources: Expert list

Created: 11 Aug 2020, 10:24 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Deafness, autosomal dominant 1, with or without thrombocytopenia, MIM# 124900

Publications

• 26912466
• 27808407]