NUP188 Biallelic Loss of Function May Underlie a New Syndrome: Nucleoporin 188 Insufficiency Syndrome?

• There is no clearly established association between the gene NUP188 and human pathology. Only a few reports of patients with different clinical presentation and different heterozygous or compound heterozygous missense or splice region variants have been identified in several sequencing projects; however, a causative association between the clinical features and the identified variants has not been established. For the first time, we report 2 unrelated patients with 2 different homozygous nonsense gene variants of NUP188, p.Tyr96* and p.Gln113*, respectively. Although having different supposedly truncating mutations, the patients presented with strikingly comparable phenotypes including pre- and postnatal microcephaly, trigonocephaly, congenital bilateral cataract, microphthalmia, cleft lip and palate or high-arched palate, camptodactyly, rocker-bottom feet, heart anomalies, specific brain changes (such as loss of periventricular white matter), thin corpus callosum, and delayed myelinization. Both patients showed very similar facial features such as laterally extended arched eyebrows, wide convex nose with a wide prominent nasal bridge, and prominent angulated antihelix. They were both born small for gestational age and died shortly after birth at the age of 67 and 140 days, respectively, as a result of central respiratory failure. Our findings strongly suggest a correlation between the homozygous nonsense gene variants of NUP188 and a severe phenotype of a new developmental syndrome with poor prognosis resulting from nucleoporin 188 homolog protein insufficiency.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Exome sequencing; Homozygous truncating mutation; New syndrome; Nucleoporin 188 insufficiency; NUP188

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