Severe microcephaly
Gene: NUP188The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.
Panel Version: 2.282
Comment on list classification: There is sufficient evidence to rate this gene Green at the next major review - progressive microcephaly reported in at least 5 affected individuals due to biallelic truncating variants in NUP188.Created: 29 Sep 2020, 10:20 a.m. | Last Modified: 29 Sep 2020, 10:20 a.m.
Panel Version: 2.25
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, 10:18 a.m. | Last Modified: 29 Sep 2020, 10:18 a.m.
Panel Version: 2.24
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Sandestig-Stefanova syndrome, 618804
Publications
Eight unrelated individuals reported.
Sources: Expert listCreated: 31 Aug 2020, 12:01 p.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
Phenotypes for gene: NUP188 were changed from Sandestig-Stefanova syndrome, 618804 to Sandestig-Stefanova syndrome, OMIM:618804
Tag for-review was removed from gene: NUP188.
Source Expert Review Green was added to NUP188. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: NUP188 were changed from microcephaly; ID; cataract; structural brain abnormalities; hypoventilation to Sandestig-Stefanova syndrome, 618804
Gene: nup188 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: NUP188.
gene: NUP188 was added gene: NUP188 was added to Severe microcephaly. 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