DOI: 10.5061/dryad.8br9852
title: Data from: PCNT point mutations and familial intracranial aneurysms

description: Objective: To identify novel genes involved in the etiology of
 intracranial aneurysms (IA) and / or subarachnoid hemorrhages (SAH) using
 whole exome sequencing. Methods. In the present study we performed whole
 exome sequencing in thirteen individuals from three families with an
 autosomal dominant IA/SAH inheritance pattern to look for candidate genes
 for disease. Additionally, we sequenced PCNT exon 38 in 161 sporadic
 IA/SAH patients in order to find additional carriers of potential
 pathogenic variants. Results. We identified two different variants in exon
 38 from the PCNT gene shared between affected members from two different
 families with either IA or SAH (p.V2811L and p.R2728C). One hundred and
 sixty four samples with either SAH or IA were Sanger sequenced for the
 PCNT exon 38. Seven missense mutations were identified. We also found a
 second p.V2811L carrier in a family with a history of neurovascular
 diseases. Conclusions. The PCNT gene encodes a protein that is involved in
 the process of microtubule nucleation and organization in interphase and
 mitosis. Biallelic loss-of-function mutations in PCNT cause a form of
 primordial dwarfism (MOPD-II) and ~50% of these patients will develop
 neurovascular abnormalities, including IAs and SAH. Additionally, a
 complete Pcnt knock-out mouse model (PcntM-/-) published previously showed
 general vascular abnormalities, including intracranial hemorrhage. The
 variants in our families lie in the highly conserved PCNT protein-protein
 interaction domain, making PCNT a highly plausible candidate gene in
 cerebrovascular disease.
description: PCNT and familial
 intracranial aneurysms-Supplemental data(1) Detailed clinical
 description of additional PCNT mutation carriers (Text). (2) Supplementary
 Table 1. Fifty five variants were shared between the two patients from
 family 7042 and absent in the healthy individuals from this family. (3)
 Supplementary Table 2. Family 7019. Variants present in patients III.2 and
 III.4 not carried by healthy individuals IV.1 and IV.2 from family 7019.
 (4) Supplementary Table 3. PCNT exon 38 primers. (5) Supplementary Table
 4. Microsatellites primers used for the haplotype sharing analysis in
 families 7019 and 8159; * = sizes based on the microsatellite analysis of
 80 Caucasian samples. (6) Supplementary Table 5. Demographic data of the
 samples used to estimate the allele frequency of customized PCNT
 microsatellite. (7) Supplementary Table 6. Mean read depth (coverage) for
 the entire PCNT gene and for exon 38 for each individual with Whole Exome
 Sequencing data. (8) Supplementary Table 7. Sixty three variants were
 shared between the two patients from family 7042 and present also in the
 healthy individuals from this family. (9) Supplementary Table 8. Sixty
 three variants were shared between the two patients from family 7019 and
 present also in the healthy individuals from this family. (10)
 Supplementary Table 9. Family 7099 PCNT variants with MAF &lt;1%. (11)
 Supplementary Figure 1. Patient 7019 III.2 CTA. (12) Supplementary Figure
 2. Patient 7042 II.1 radiologic studies. (13) Supplementary Figure 3.
 Patient 7099 II.2 radiologic studies. (14) Supplementary Figure 4. Patient
 8080 II.2 radiologic studies. (15) Supplementary Figure 5. Patient 8091
 III.1 radiologic studies. (16) Supplementary Figure 6. Patient 8159 III.3
 CTA. (17) Supplementary Figure 7. Haplotype reconstruction for families
 7019 and 8159 sharing mutation p.Val2821Leu. (18) Supplementary Figure 8.
 Coding isoforms and processed transcripts of PCNT gene. (19) Supplementary
 Figure 9. Phylogenetic tree depicting evolutionary relationship of PCNT
 gene across species. (20) Supplementary Figure 10. A. PCNT gene
 conservation.Resub - PCNT point mutations
 and familial intracranial aneurysms -
 Suppl_Neurology.pdf