Bio

Bio


Jillian is a board-certified Clinical Molecular Geneticist working in Stanford Medicine’s Clinical Genomics Program (CGP). She completed a research-based MS at University College Dublin in Ireland and later received her PhD in Molecular Genetics and Genomics in 2014 from Washington University in St. Louis. After her PhD, Jillian joined Harvard Medical School's Genetics Training Program and completed her fellowship in Clinical Molecular Genetics in 2016. Jillian then joined the Department of Pathology at Stanford School of Medicine and became board-certified by the American Board of Medical Genetics and Genomics in 2017. Her focus is on molecular-based diagnostic testing, with the majority of her time spent in the CGP, where she oversees overall laboratory operations, development of new next-generation sequencing-based clinical assays, ensures CAP/CLIA regulatory compliance, and signs out clinical test reports. She and her team launched Stanford's first clinical exome sequencing test, and the first test for the newly created CGP, in early 2018.

Clinical Focus


  • Genetics
  • Pathology
  • Genomics

Academic Appointments


  • Clinical Assistant Professor, Pathology

Administrative Appointments


  • Associate Program Director, Laboratory Genetics and Genomics Training Program (2019 - Present)
  • Assistant Laboratory Director, Stanford Medicine Clinical Genomics Program (2016 - Present)

Boards, Advisory Committees, Professional Organizations


  • Diplomate (Clinical Molecular Genetics), American Board of Medical Genetics and Genomics (2017 - Present)
  • Contributor, Clinical & Laboratory Standards Institute Document Development Committee on Nucleic Acid Sequencing (MM09) (2018 - Present)
  • Fellow, American College of Medical Genetics and Genomics (2018 - Present)

Professional Education


  • Fellowship, Harvard Medical School, ABMGG Clinical Molecular Genetics Fellowship (2016)
  • PhD, Washington University in St. Louis, Molecular Genetics and Genomics (2014)
  • MS, University College Dublin, Research-based (2010)
  • BS, University of Washington, Molecular Cellular and Developmental Biology (2008)

Publications

All Publications


  • Rapid Genome Sequencing in the Critically Ill CLINICAL CHEMISTRY Buchan, J. G., White, S., Joshi, R., Ashley, E. A. 2019; 65 (6): 723–26
  • Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel GENETICS IN MEDICINE Kelly, M. A., Caleshu, C., Morales, A., Buchan, J., Wolf, Z., Harrison, S. M., Cook, S., Dillon, M. W., Garcia, J., Haverfield, E., Jongbloed, J. H., Macaya, D., Manrai, A., Orland, K., Richard, G., Spoonamore, K., Thomas, M., Thomson, K., Vincent, L. M., Walsh, R., Watkins, H., Whiffin, N., Ingles, J., van Tintelen, J., Semsarian, C., Ware, J. S., Hershberger, R., Funke, B., ClinGen Cardiovasc Clinical Domain 2018; 20 (3): 351–59

    Abstract

    PurposeIntegrating genomic sequencing in clinical care requires standardization of variant interpretation practices. The Clinical Genome Resource has established expert panels to adapt the American College of Medical Genetics and Genomics/Association for Molecular Pathology classification framework for specific genes and diseases. The Cardiomyopathy Expert Panel selected MYH7, a key contributor to inherited cardiomyopathies, as a pilot gene to develop a broadly applicable approach.MethodsExpert revisions were tested with 60 variants using a structured double review by pairs of clinical and diagnostic laboratory experts. Final consensus rules were established via iterative discussions.ResultsAdjustments represented disease-/gene-informed specifications (12) or strength adjustments of existing rules (5). Nine rules were deemed not applicable. Key specifications included quantitative frameworks for minor allele frequency thresholds, the use of segregation data, and a semiquantitative approach to counting multiple independent variant occurrences where fully controlled case-control studies are lacking. Initial inter-expert classification concordance was 93%. Internal data from participating diagnostic laboratories changed the classification of 20% of the variants (n = 12), highlighting the critical importance of data sharing.ConclusionThese adapted rules provide increased specificity for use in MYH7-associated disorders in combination with expert review and clinical judgment and serve as a stepping stone for genes and disorders with similar genetic and clinical characteristics.

    View details for PubMedID 29300372

    View details for PubMedCentralID PMC5876064

  • Canine MAS1: monoallelic expression is suggestive of an imprinted gene. Animal genetics Nolan, C. M., Shiel, R. E., Buchan, J. G., O'Sullivan, F. M., Callanan, J. J. 2018; 49 (5): 438–46

    Abstract

    Imprinted genes are epigenetically modified in a parent-of-origin dependent manner and as a consequence are differentially expressed, with one allele typically expressed while the other is repressed. In canine, the insulin like growth factor 2 receptor gene (IGF2R) is imprinted with predominant expression of the maternally inherited allele. Because imprinted genes usually occur in clusters, we examined the allelic expression pattern of the gene encoding the canine Mas receptor (MAS1), which is located upstream of IGF2R on canine chromosome 1 and is highly conserved in mammals. In this report we describe monoallelic expression of canine MAS1 in the neonatal umbilical cord of several individuals and we identify the expressed allele as maternally inherited. These data suggest that canine MAS1 is an imprinted gene.

    View details for DOI 10.1111/age.12705

    View details for PubMedID 30062832

  • Long-read genome sequencing identifies causal structural variation in a Mendelian disease. Genetics in medicine : official journal of the American College of Medical Genetics Merker, J. D., Wenger, A. M., Sneddon, T., Grove, M., Zappala, Z., Fresard, L., Waggott, D., Utiramerur, S., Hou, Y., Smith, K. S., Montgomery, S. B., Wheeler, M., Buchan, J. G., Lambert, C. C., Eng, K. S., Hickey, L., Korlach, J., Ford, J., Ashley, E. A. 2017

    Abstract

    PurposeCurrent clinical genomics assays primarily utilize short-read sequencing (SRS), but SRS has limited ability to evaluate repetitive regions and structural variants. Long-read sequencing (LRS) has complementary strengths, and we aimed to determine whether LRS could offer a means to identify overlooked genetic variation in patients undiagnosed by SRS.MethodsWe performed low-coverage genome LRS to identify structural variants in a patient who presented with multiple neoplasia and cardiac myxomata, in whom the results of targeted clinical testing and genome SRS were negative.ResultsThis LRS approach yielded 6,971 deletions and 6,821 insertions > 50 bp. Filtering for variants that are absent in an unrelated control and overlap a disease gene coding exon identified three deletions and three insertions. One of these, a heterozygous 2,184 bp deletion, overlaps the first coding exon of PRKAR1A, which is implicated in autosomal dominant Carney complex. RNA sequencing demonstrated decreased PRKAR1A expression. The deletion was classified as pathogenic based on guidelines for interpretation of sequence variants.ConclusionThis first successful application of genome LRS to identify a pathogenic variant in a patient suggests that LRS has significant potential for the identification of disease-causing structural variation. Larger studies will ultimately be required to evaluate the potential clinical utility of LRS.GENETICS in MEDICINE advance online publication, 22 June 2017; doi:10.1038/gim.2017.86.

    View details for PubMedID 28640241

  • Kinesin family member 6 (kif6) is necessary for spine development in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists Buchan, J. G., Gray, R. S., Gansner, J. M., Alvarado, D. M., Burgert, L., Gitlin, J. D., Gurnett, C. A., Goldsmith, M. I. 2014; 243 (12): 1646–57

    Abstract

    Idiopathic scoliosis is a form of spinal deformity that affects 2-3% of children and results in curvature of the spine without structural defects of the vertebral units. The pathogenesis of idiopathic scoliosis remains poorly understood, in part due to the lack of a relevant animal model.We performed a forward mutagenesis screen in zebrafish to identify new models for idiopathic scoliosis. We isolated a recessive zebrafish mutant, called skolios, which develops isolated spinal curvature that arises independent of vertebral malformations. Using meiotic mapping and whole genome sequencing, we identified a nonsense mutation in kinesin family member 6 (kif6(gw326) ) unique to skolios mutants. Three additional kif6 frameshift alleles (gw327, gw328, gw329) were generated with transcription activator-like effector nucleases (TALENs). Zebrafish homozygous or compound heterozygous for kif6 frameshift mutations developed a scoliosis phenotype indistinguishable from skolios mutants, confirming that skolios is caused by the loss of kif6. Although kif6 may play a role in cilia, no evidence for cilia dysfunction was seen in kif6(gw326) mutants.Overall, these findings demonstrate a novel role for kif6 in spinal development and identify a new candidate gene for human idiopathic scoliosis.

    View details for DOI 10.1002/dvdy.24208

    View details for PubMedID 25283277

    View details for PubMedCentralID PMC6207368

  • Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis. Human molecular genetics Buchan, J. G., Alvarado, D. M., Haller, G. E., Cruchaga, C., Harms, M. B., Zhang, T., Willing, M. C., Grange, D. K., Braverman, A. C., Miller, N. H., Morcuende, J. A., Tang, N. L., Lam, T. P., Ng, B. K., Cheng, J. C., Dobbs, M. B., Gurnett, C. A. 2014; 23 (19): 5271–82

    Abstract

    Adolescent idiopathic scoliosis (AIS) causes spinal deformity in 3% of children. Despite a strong genetic basis, few genes have been associated with AIS and the pathogenesis remains poorly understood. In a genome-wide rare variant burden analysis using exome sequence data, we identified fibrillin-1 (FBN1) as the most significantly associated gene with AIS. Based on these results, FBN1 and a related gene, fibrillin-2 (FBN2), were sequenced in a total of 852 AIS cases and 669 controls. In individuals of European ancestry, rare variants in FBN1 and FBN2 were enriched in severely affected AIS cases (7.6%) compared with in-house controls (2.4%) (OR = 3.5, P = 5.46 × 10(-4)) and Exome Sequencing Project controls (2.3%) (OR = 3.5, P = 1.48 × 10(-6)). Scoliosis severity in AIS cases was associated with FBN1 and FBN2 rare variants (P = 0.0012) and replicated in an independent Han Chinese cohort (P = 0.0376), suggesting that rare variants may be useful as predictors of curve progression. Clinical evaluations revealed that the majority of AIS cases with rare FBN1 variants do not meet diagnostic criteria for Marfan syndrome, though variants are associated with tall stature (P = 0.0035) and upregulation of the transforming growth factor beta pathway. Overall, these results expand our definition of fibrillin-related disorders to include AIS and open up new strategies for diagnosing and treating severe AIS.

    View details for DOI 10.1093/hmg/ddu224

    View details for PubMedID 24833718

    View details for PubMedCentralID PMC4159151

  • Are copy number variants associated with adolescent idiopathic scoliosis? Clinical orthopaedics and related research Buchan, J. G., Alvarado, D. M., Haller, G., Aferol, H., Miller, N. H., Dobbs, M. B., Gurnett, C. A. 2014; 472 (10): 3216–25

    Abstract

    Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder that causes spinal deformity in approximately 3% of the population. Candidate gene, linkage, and genome-wide association studies have sought to identify genetic variation that predisposes individuals to AIS, but the genetic basis remains unclear. Copy number variants are associated with several isolated skeletal phenotypes, but their role in AIS, to our knowledge, has not been assessed.We determined the frequency of recurrent copy number rearrangements, chromosome aneuploidy, and rare copy number variants in patients with AIS.Between January 2010 and August 2014, we evaluated 150 patients with isolated AIS and spinal curvatures measuring 10° or greater, and 148 agreed to participate. Genomic copy number analysis was performed on patients and 1079 control subjects using the Affymetrix(®) Genome-wide Human SNP Array 6.0. After removing poor quality samples, 143 (97%) patients with AIS were evaluated for copy number variation.We identified a duplication of chromosome 1q21.1 in 2.1% (N = 3/143) of patients with AIS, which was enriched compared with 0.09% (N = 1/1079) of control subjects (p = 0.0057) and 0.07% (N = 6/8329) of a large published control cohort (p = 0.0004). Other notable findings include trisomy X, which was identified in 1.8% (N = 2/114) of female patients with AIS, and rearrangements of chromosome 15q11.2 and 16p11.2 that previously have been associated with spinal phenotypes. Finally, we report rare copy number variants that will be useful in future studies investigating candidate genes for AIS.Copy number variation and chromosomal aneuploidy may contribute to the pathogenesis of adolescent idiopathic scoliosis.Chromosomal microarray may reveal clinically useful abnormalities in some patients with AIS.

    View details for DOI 10.1007/s11999-014-3766-8

    View details for PubMedID 25005481

    View details for PubMedCentralID PMC4160470

  • Copy number analysis of 413 isolated talipes equinovarus patients suggests role for transcriptional regulators of early limb development EUROPEAN JOURNAL OF HUMAN GENETICS Alvarado, D. M., Buchan, J. G., Frick, S. L., Herzenberg, J. E., Dobbs, M. B., Gurnett, C. A. 2013; 21 (4): 373-380

    Abstract

    Talipes equinovarus is one of the most common congenital musculoskeletal anomalies and has a worldwide incidence of 1 in 1000 births. A genetic predisposition to talipes equinovarus is evidenced by the high concordance rate in twin studies and the increased risk to first-degree relatives. Despite the frequency of isolated talipes equinovarus and the strong evidence of a genetic basis for the disorder, few causative genes have been identified. To identify rare and/or recurrent copy number variants, we performed a genome-wide screen for deletions and duplications in 413 isolated talipes equinovarus patients using the Affymetrix 6.0 array. Segregation analysis within families and gene expression in mouse E12.5 limb buds were used to determine the significance of copy number variants. We identified 74 rare, gene-containing copy number variants that were present in talipes equinovarus probands and not present in 759 controls or in the Database of Genomic Variants. The overall frequency of copy number variants was similar between talipes equinovarus patients compared with controls. Twelve rare copy number variants segregate with talipes equinovarus in multiplex pedigrees, and contain the developmentally expressed transcription factors and transcriptional regulators PITX1, TBX4, HOXC13, UTX, CHD (chromodomain protein)1, and RIPPLY2. Although our results do not support a major role for recurrent copy number variations in the etiology of isolated talipes equinovarus, they do suggest a role for genes involved in early embryonic patterning in some families that can now be tested with large-scale sequencing methods.

    View details for DOI 10.1038/ejhg.2012.177

    View details for Web of Science ID 000317089300005

    View details for PubMedID 22892537

    View details for PubMedCentralID PMC3598331

  • MYBPC1 mutations impair skeletal muscle function in zebrafish models of arthrogryposis. Human molecular genetics Ha, K., Buchan, J. G., Alvarado, D. M., McCall, K., Vydyanath, A., Luther, P. K., Goldsmith, M. I., Dobbs, M. B., Gurnett, C. A. 2013; 22 (24): 4967–77

    Abstract

    Myosin-binding protein C1 (MYBPC1) is an abundant skeletal muscle protein that is expressed predominantly in slow-twitch muscle fibers. Human MYBPC1 mutations are associated with distal arthrogryposis type 1 and lethal congenital contracture syndrome type 4. As MYBPC1 function is incompletely understood, the mechanism by which human mutations result in contractures is unknown. Here, we demonstrate using antisense morpholino knockdown, that mybpc1 is required for embryonic motor activity and survival in a zebrafish model of arthrogryposis. Mybpc1 morphant embryos have severe body curvature, cardiac edema, impaired motor excitation and are delayed in hatching. Myofibril organization is selectively impaired in slow skeletal muscle and sarcomere numbers are greatly reduced in mybpc1 knockdown embryos, although electron microscopy reveals normal sarcomere structure. To evaluate the effects of human distal arthrogryposis mutations, mybpc1 mRNAs containing the corresponding human W236R and Y856H MYBPC1 mutations were injected into embryos. Dominant-negative effects of these mutations were suggested by the resultant mild bent body curvature, decreased motor activity, as well as impaired overall survival compared with overexpression of wild-type RNA. These results demonstrate a critical role for mybpc1 in slow skeletal muscle development and establish zebrafish as a tractable model of human distal arthrogryposis.

    View details for DOI 10.1093/hmg/ddt344

    View details for PubMedID 23873045

    View details for PubMedCentralID PMC3836476

  • Polygenic threshold model with sex dimorphism in adolescent idiopathic scoliosis: the Carter effect. The Journal of bone and joint surgery. American volume Kruse, L. M., Buchan, J. G., Gurnett, C. A., Dobbs, M. B. 2012; 94 (16): 1485–91

    Abstract

    Adolescent idiopathic scoliosis occurs between two and ten times more frequently in females than in males. The exact cause of this sex discrepancy is unknown, but it may represent a difference in susceptibility to the deformity. If this difference is attributable to genetic factors, then males with adolescent idiopathic scoliosis would need to inherit a greater number of susceptibility genes compared with females to develop the deformity. Males would also be more likely to transmit the disease to their children and to have siblings with adolescent idiopathic scoliosis. Such a phenomenon is known as the Carter effect, and the presence of such an effect would support a multifactorial threshold model of inheritance.One hundred and forty multiplex families in which more than one individual was affected with adolescent idiopathic scoliosis were studied. These families contained 1616 individuals, including 474 individuals with adolescent idiopathic scoliosis and 1142 unaffected relatives. The rates of transmission from the 122 affected mothers and from the twenty-eight affected fathers were calculated, and the prevalence among siblings was determined in the nuclear families of affected individuals.The prevalence of adolescent idiopathic scoliosis in these multiplex families was lowest in sons of affected mothers (36%, thirty-eight of 105) and highest in daughters of affected fathers (85%, twenty-two of twenty-six). Affected fathers transmitted adolescent idiopathic scoliosis to 80% (thirty-seven) of forty-six children, whereas affected mothers transmitted it to 56% (133) of 239 children (p < 0.001). Siblings of affected males also had a significantly higher prevalence of adolescent idiopathic scoliosis (55%, sixty-one of 110) compared with siblings of affected females (45%, 206 of 462) (p = 0.04).This study demonstrates the presence of the Carter effect in adolescent idiopathic scoliosis. This pattern can be explained by polygenic inheritance of adolescent idiopathic scoliosis, with a greater genetic load required for males to be affected.

    View details for DOI 10.2106/JBJS.K.01450

    View details for PubMedID 22992817

  • Exome sequencing identifies an MYH3 mutation in a family with distal arthrogryposis type 1. The Journal of bone and joint surgery. American volume Alvarado, D. M., Buchan, J. G., Gurnett, C. A., Dobbs, M. B. 2011; 93 (11): 1045–50

    Abstract

    Few genes responsible for distal arthrogryposis type 1 are known, although genes coding for the proteins in the sarcomere have been implicated in other types of distal arthrogryposis. Cost-effective sequencing methods are now available to examine all genes in the human genome for the purpose of establishing the genetic basis of musculoskeletal disorders.A multigenerational family with distal arthrogryposis type 1 characterized by clubfoot and mild hand contractures was identified, and exome sequencing was performed on DNA from one of the affected family members. Linkage analysis was used to confirm whether a genetic variant segregated with distal arthrogryposis.Exome sequencing identified 573 novel variants that were not present in control databases. A missense mutation in MYH3 (a gene coding for the heavy chain of myosin), causing an F437I amino acid substitution, was identified that segregated with distal arthrogryposis in this family. Linkage analysis confirmed that this MYH3 mutation was the only exome variant common to all six affected individuals.Identification of an MYH3 mutation in this family with distal arthrogryposis type 1 broadens the phenotype associated with MYH3 mutations to include distal arthrogryposis types 1, 2A (Freeman-Sheldon syndrome), and 2B (Sheldon-Hall syndrome). Exome sequencing is a useful and cost-effective method to discover causative genetic mutations, although data from extended families may be needed to confirm the importance of the hundreds of identified variants.

    View details for DOI 10.2106/JBJS.J.02004

    View details for PubMedID 21531865

    View details for PubMedCentralID PMC3102311

  • Familial isolated clubfoot is associated with recurrent chromosome 17q23.1q23.2 microduplications containing TBX4. American journal of human genetics Alvarado, D. M., Aferol, H., McCall, K., Huang, J. B., Techy, M., Buchan, J., Cady, J., Gonzales, P. R., Dobbs, M. B., Gurnett, C. A. 2010; 87 (1): 154–60

    Abstract

    Clubfoot is a common musculoskeletal birth defect for which few causative genes have been identified. To identify the genes responsible for isolated clubfoot, we screened for genomic copy-number variants with the Affymetrix Genome-wide Human SNP Array 6.0. A recurrent chromosome 17q23.1q23.2 microduplication was identified in 3 of 66 probands with familial isolated clubfoot. The chromosome 17q23.1q23.2 microduplication segregated with autosomal-dominant clubfoot in all three families but with reduced penetrance. Mild short stature was common and one female had developmental hip dysplasia. Subtle skeletal abnormalities consisted of broad and shortened metatarsals and calcanei, small distal tibial epiphyses, and thickened ischia. Several skeletal features were opposite to those described in the reciprocal chromosome 17q23.1q23.2 microdeletion syndrome associated with developmental delay and cardiac and limb abnormalities. Of note, during our study, we also identified a microdeletion at the locus in a sibling pair with isolated clubfoot. The chromosome 17q23.1q23.2 region contains the T-box transcription factor TBX4, a likely target of the bicoid-related transcription factor PITX1 previously implicated in clubfoot etiology. Our result suggests that this chromosome 17q23.1q23.2 microduplication is a relatively common cause of familial isolated clubfoot and provides strong evidence linking clubfoot etiology to abnormal early limb development.

    View details for DOI 10.1016/j.ajhg.2010.06.010

    View details for PubMedID 20598276

    View details for PubMedCentralID PMC2896772

  • SEPT9 gene sequencing analysis reveals recurrent mutations in hereditary neuralgic amyotrophy. Neurology Hannibal, M. C., Ruzzo, E. K., Miller, L. R., Betz, B., Buchan, J. G., Knutzen, D. M., Barnett, K., Landsverk, M. L., Brice, A., LeGuern, E., Bedford, H. M., Worrall, B. B., Lovitt, S., Appel, S. H., Andermann, E., Bird, T. D., Chance, P. F. 2009; 72 (20): 1755–59

    Abstract

    Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder that manifests as recurrent, episodic, painful brachial neuropathies. A gene for HNA maps to chromosome 17q25.3 where mutations in SEPT9, encoding the septin-9 protein, have been identified.To determine the frequency and type of mutations in the SEPT9 gene in a new cohort of 42 unrelated HNA pedigrees.DNA sequencing of all exons and intron-exon boundaries for SEPT9 was carried out in an affected individual in each pedigree from our HNA cohort. Genotyping using microsatellite markers spanning the SEPT9 gene was also used to identify pedigrees with a previously reported founder haplotype.Two missense mutations were found: c.262C>T (p.Arg88Trp) in seven HNA pedigrees and c.278C>T (p.Ser93Phe) in one HNA pedigree. Sequencing of other known exons in SEPT9 detected no additional disease-associated mutations. A founder haplotype, without defined mutations in SEPT9, was present in seven pedigrees.We provide further evidence that mutation of the SEPT9 gene is the molecular basis of some cases of hereditary neuralgic amyotrophy (HNA). DNA sequencing of SEPT9 demonstrates a restricted set of mutations in this cohort of HNA pedigrees. Nonetheless, sequence analysis will have an important role in mutation detection in HNA. Additional techniques will be required to find SEPT9 mutations in an HNA founder haplotype and other pedigrees.

    View details for DOI 10.1212/WNL.0b013e3181a609e3

    View details for PubMedID 19451530

    View details for PubMedCentralID PMC2683739

  • Duplication within the SEPT9 gene associated with a founder effect in North American families with hereditary neuralgic amyotrophy. Human molecular genetics Landsverk, M. L., Ruzzo, E. K., Mefford, H. C., Buysse, K., Buchan, J. G., Eichler, E. E., Petty, E. M., Peterson, E. A., Knutzen, D. M., Barnett, K., Farlow, M. R., Caress, J., Parry, G. J., Quan, D., Gardner, K. L., Hong, M., Simmons, Z., Bird, T. D., Chance, P. F., Hannibal, M. C. 2009; 18 (7): 1200–1208

    Abstract

    Hereditary neuralgic amyotrophy (HNA) is an autosomal dominant disorder associated with recurrent episodes of focal neuropathy primarily affecting the brachial plexus. Point mutations in the SEPT9 gene have been previously identified as the molecular basis of HNA in some pedigrees. However in many families, including those from North America demonstrating a genetic founder haplotype, no sequence mutations have been detected. We report an intragenic 38 Kb SEPT9 duplication that is linked to HNA in 12 North American families that share the common founder haplotype. Analysis of the breakpoints showed that the duplication is identical in all pedigrees, and molecular analysis revealed that the duplication includes the 645 bp exon in which previous HNA mutations were found. The SEPT9 transcript variants that span this duplication contain two in-frame repeats of this exon, and immunoblotting demonstrates larger molecular weight SEPT9 protein isoforms. This exon also encodes for a majority of the SEPT9 N-terminal proline rich region suggesting that this region plays a role in the pathogenesis of HNA.

    View details for DOI 10.1093/hmg/ddp014

    View details for PubMedID 19139049

    View details for PubMedCentralID PMC2722193