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Cataracts

Gene: NUP188

Amber List (moderate evidence)

NUP188 (nucleoporin 188)
EnsemblGeneIds (GRCh38): ENSG00000095319
EnsemblGeneIds (GRCh37): ENSG00000095319
OMIM: 615587, Gene2Phenotype
NUP188 is in 4 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence to rate this gene Green at the next major review - congenital cataract reported in at least 6 affected individuals (5 unrelated kindreds) due to biallelic truncating variants in NUP188.
Created: 29 Sep 2020, 10:17 a.m. | Last Modified: 29 Sep 2020, 10:17 a.m.
Panel Version: 2.14
Associated with Sandestig-Stefanova syndrome in OMIM, but not yet in G2P.

- PMID: 32021605 (2020) - Two unrelated patients with different homozygous nonsense variants of NUP188, c.287dupA, p.Tyr96* and c.337C>T, p.Gln113*, respectively. Authors note strikingly comparable phenotypes including pre- and postnatal microcephaly, trigonocephaly, congenital cataract, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, ventricular septal defect, and brain MRI anomalies (ventriculomegaly, loss of periventricular white matter, thin corpus callosum, and delayed myelination). Both ultimately died as a result of central respiratory failure at the age of 67 and 140 days, respectively.

- PMID: 32275884 (2020) - Six individuals from four unrelated families with bi-allelic truncating variants in NUP188 and similar phenotypes characterised by prenatal-onset ventriculomegaly or suspected brain malformation (4/6), congenital cataracts (4/6), congenital heart defects (5/5), hypotonia (5/6), brain MRI abnormalities (6/6) including ventriculomegaly loss of white-matter, hypoplastic corpus callosum, and delayed myelination. Progressive microcephaly consistent with a neurodegenerative process was noted in at least 3 cases. All six patients died of respiratory failure or respiratory-related illness: five within the first seven months of life; and the sixth at 2 years and 7 months, who also has severe ID and was non-ambulatory.
Created: 29 Sep 2020, 10:12 a.m. | Last Modified: 29 Sep 2020, 10:12 a.m.
Panel Version: 2.13

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sandestig-Stefanova syndrome, 618804

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

8 unrelated individuals reported with bi-allelic variants and a neurodevelopmental phenotype with cataracts.
Sources: Expert list
Created: 8 Jul 2020, 8:10 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
microcephaly; ID; cataract; structural brain abnormalities; hypoventilation

Publications

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

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Sandestig-Stefanova syndrome, 618804
Tags
for-review
OMIM
615587
Clinvar variants
Variants in NUP188
Penetrance
None
Publications
Panels with this gene

History Filter Activity

29 Sep 2020, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract; structural brain abnormalities; hypoventilation to Sandestig-Stefanova syndrome, 618804

29 Sep 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: nup188 has been classified as Amber List (Moderate Evidence).

29 Sep 2020, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: NUP188.

8 Jul 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: NUP188 was added gene: NUP188 was added to Cataracts. Sources: Expert list Mode of inheritance for gene: NUP188 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NUP188 were set to 32021605; 28726809; 32275884 Phenotypes for gene: NUP188 were set to microcephaly; ID; cataract; structural brain abnormalities; hypoventilation Review for gene: NUP188 was set to GREEN gene: NUP188 was marked as current diagnostic