ICNC Abstracts, ICNC 2018

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Two distinct phenotypes caused by the same mutation in the SAMHD1 gene
Serdal Gungor, Derya Okur, Elmasnur Yilmaz, Ana Topf, Rita Horvath, Hanns Lochmuller, Bilge Ozgor, Ece Sonmezler, Uluc Yis, Ahmet Yaramis, Yavuz Oktay, Semra Hiz

Last modified: 2018-09-09


Introduction:SAMHD1 is a gene associated with Aicardi-Goutieres syndrome type-5, a genetic autoimmune disorder that mimics congenital viral infection and is characterized by the aberrant production of type-I interferons(OMIM#612952). Here we present two different patients with distinct phenotypes that have same SAMHD1 mutation.

Patients:First case was a 5-year-old male patient with recurrent strokes. His neurological examination revealed hemiplegia with increased deep tendon reflexes. Cranial CT showed bilateral basal ganglia calcifications. Diffusion-weighted MRI showed restricted diffusion and MR-angiography revealed narrowing of middle and anterior cerebral artery (Figures 1,2).

The second case, a 3-year-old male, presented developmental delay and epilepsy. His physical examination revealed dysmorphic facial features, hypotonia and spastic quadriplegia with hyperreflexia and dystonia. Brain MRI showed periventricular white matter T2 hyperintensities resembling leukodystrophy. In the scope of the CONSEQUITUR, a multinational project that focuses on undiagnosed neuropediatric patients born to consanguineous parents, WES was performed by Broad Institute, MIT-Harvard. Data analysis was carried out on the RD-Connect Platform. The same homozygous stop-gain mutation (c.490C>T,p.Arg164*) in exon4 of SAMHD1 was identified in both of the patients. The Arg164* had previously been annotated as a disease-causing variant in a compound heterozygous state (rs267607027)(CADD=39) and is extremely rare(gnomAD Exomes AF=0.000004061).

Conclusion:These results show that a stop-gain mutation in SAMHD1 can cause clinically distinct phenotypes. In addition to the phenotypic heterogeneity, occurrence of the exact same rare mutation in two seemingly unrelated cases from the Eastern part of Turkey imply it possibly as a founder mutation for this region.

(This study is funded by TUBITAK-216S771)


SAMHD1 gene; Aicardi-Goutrieres syndrome; WES

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