White matter disorders and cerebral calcification - narrow panel

Gene: NUP188

The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.

Created: 9 Mar 2022, 4:29 p.m. | Last Modified: 9 Mar 2022, 4:29 p.m.

Panel Version: 1.223

Green List (high evidence)

Comment on list classification: There is sufficient evidence to rate this gene Green at the next major review - abnormalities on brain MRI are reported in all affected individuals to date, including loss of white matter (4/8) and delayed myelination (5/8)

Created: 29 Sep 2020, 10:34 a.m. | Last Modified: 29 Sep 2020, 10:34 a.m.

Panel Version: 1.16

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.
Sources: Literature

Created: 29 Sep 2020, 10:26 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sandestig-Stefanova syndrome, 618804

Publications

• 32021605
• 32275884