Genetics and genomic medicine in the Philippines
. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - September 15, 2016 Category: Genetics & Stem Cells Authors: Carmencita D. Padilla, Eva Maria Cutiongco ‐de la Paz Tags: Genetics and Genomic Medicine around the World Source Type: research

hg19K: addressing a significant lacuna in hg19 ‐based variant calling
ConclusionWe report that the presence of minor alleles in hg19 alone results in ~8% false negatives and ~30% false positives during variant calls. Also, among the variant calls unique to hg19K‐based methods, which are missed in individuals homozygous to the minor alleles in hg19‐based prediction, some are deleterious missense mutations at sites conserved across diverse species. According to the 1000 genomes project, roughly two million positions in hg19 are minor alleles. Current variant calling methods will mask these SNVs in individuals who are homozygous to these alleles. Using hg19K, which is a mosaic of major all...
Source: Molecular Genetics & Genomic Medicine - September 1, 2016 Category: Genetics & Stem Cells Authors: Savita Karthikeyan, Pushpinder S. Bawa, Subhashini Srinivasan Tags: Original Article Source Type: research

Genetics and genomic medicine in Morocco: the present hope can make the future bright
. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - September 1, 2016 Category: Genetics & Stem Cells Authors: Khadija Belhassan, Karim Ouldim, Abdel Aziz Sefiani Tags: Genetics and Genomic Medicine around the World Source Type: research

Aneuploidy screening using circulating fetal cells in maternal blood by dual ‐probe FISH protocol: a prospective feasibility study on a series of 172 pregnant women
ConclusionsNoninvasive prenatal aneuploidy screening using fetal cells isolated from maternal blood is feasible and could substantially reduce the need for invasive procedures. One hundred and seventy‐two pregnant women received prospective testing for fetal aneuploidy by applying our recently established dual‐probe FISH protocol to fetal cells isolated and enriched from maternal blood. Seven out of 172 samples showed a fetal aneuploidy which was confirmed by invasive prenatal diagnosis procedures. The frequency of trisomic cells (range 0.38–0.90%) for samples from aneuploid pregnancies was at least double that ...
Source: Molecular Genetics & Genomic Medicine - September 1, 2016 Category: Genetics & Stem Cells Authors: Giuseppe Calabrese, Donatella Fantasia, Melissa Alfonsi, Elisena Morizio, Claudio Celentano, Paolo Guanciali Franchi, Giulia Sabbatinelli, Chiara Palka, Peter Benn, Gianmaria Sitar Tags: Original Article Source Type: research

How, who, and when: preferences for delivery of genome sequencing results among women diagnosed with breast cancer at a young age
ConclusionsA critical goal for future transdisciplinary research including clinicians, patients, and communication researchers may be to develop decision‐making processes to help patients make decisions about how they would like various sequencing results returned. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - September 1, 2016 Category: Genetics & Stem Cells Authors: Kimberly A. Kaphingst, Jennifer Ivanovich, Ashley Elrick, Rebecca Dresser, Cindy Matsen, Melody S. Goodman Tags: Original Article Source Type: research

Ultrastructure of early amelogenesis in wild ‐type, Amelx‐/‐, and Enam‐/‐ mice: enamel ribbon initiation on dentin mineral and ribbon orientation by ameloblasts
ConclusionAmelogenin does not directly nucleate, shape, or orient enamel ribbons, but separates and supports the enamel ribbons, and expands the enamel matrix to accommodate continued ribbon elongation, retrograde ameloblast movement, and rod/interrod organization. This is the first report using focused ion beam microscopy to visualize enamel ribbons at high resolution as they form, which are shown to initiate on the underlying dentin crystals. This continuity between dentin and enamel mineral has been difficult to establish with conventional thin sectioning techniques and has been debated for many years. We converted ser...
Source: Molecular Genetics & Genomic Medicine - September 1, 2016 Category: Genetics & Stem Cells Authors: Charles E. Smith, Yuanyuan Hu, Jan C. ‐C. Hu, James P. Simmer Tags: Original Article Source Type: research

Enamel ribbons, surface nodules, and octacalcium phosphate in C57BL/6 Amelx −/− mice and Amelx+/− lyonization
ConclusionAmelogenin forms a resorbable matrix that separates and supports, but does not shape early secretory‐stage enamel ribbons. Amelogenin may facilitate the conversion of enamel ribbons into hydroxyapatite by inhibiting the formation of octacalcium phosphate. Amelogenin is necessary for thickening the enamel layer, which helps maintain ribbon organization and development and maintenance of the Tomes’ process. We thoroughly characterized enamel formation in amelogenin null mice and determined that the mineral covering dentin in these animals is octacalcium phosphate. The initial enamel mineral has a ribbon sh...
Source: Molecular Genetics & Genomic Medicine - September 1, 2016 Category: Genetics & Stem Cells Authors: Yuanyuan Hu, Charles E. Smith, Zhonghou Cai, Lorenza A. ‐J. Donnelly, Jie Yang, Jan C.‐C. Hu, James P. Simmer Tags: Original Article Source Type: research

Rare variants in optic disc area gene CARD10 enriched in primary open ‐angle glaucoma
ConclusionWe report here an enrichment of rare predicted pathogenic coding variants within a GWAS‐associated locus in POAG (CARD10). These findings indicate that both common and rare pathogenic coding variants in CARD10 may contribute to POAG pathogenesis. Genome‐wide association studies (GWAS) have identified association of common alleles with primary open‐angle glaucoma (POAG) and its quantitative endophenotypes near numerous genes. This study utilizes whole exome sequencing in a cohort of advanced POAG participants to examine the contribution of rare variants in those GWAS‐associated genes. We find that rare va...
Source: Molecular Genetics & Genomic Medicine - September 1, 2016 Category: Genetics & Stem Cells Authors: Tiger Zhou, Emmanuelle Souzeau, Shiwani Sharma, Owen M. Siggs, Ivan Goldberg, Paul R. Healey, Stuart Graham, Alex W. Hewitt, David A. Mackey, Robert J. Casson, John Landers, Richard Mills, Jonathan Ellis, Paul Leo, Matthew A. Brown, Stuart MacGregor, Kath Tags: Original Article Source Type: research

A patient with lissencephaly, developmental delay, and infantile spasms, due to de novo heterozygous mutation of KIF2A
ConclusionFindings support the pathogenic link between KIF2A mutation and lissencephaly, and expand the range of presentation to include infantile spasms and congenital anomalies. Microtubules play critical roles in cerebral cortical development and mutations in genes that encode tubulins or a spectrum of proteins involved in the regulation of microtubule dynamics lead to malformations of cortical development including lissencephaly. Here, we describe a patient with lissencephaly, developmental delay, nystagmus, persistent hyperplastic primary vitreous, and infantile spasms, found to have a novel de novo mutation in kines...
Source: Molecular Genetics & Genomic Medicine - September 1, 2016 Category: Genetics & Stem Cells Authors: Guoling Tian, Ana G. Cristancho, Holly A. Dubbs, Grant T. Liu, Nicholas J. Cowan, Ethan M. Goldberg Tags: Original Article Source Type: research

A potential founder variant in CARMIL2/RLTPR in three Norwegian families with warts, molluscum contagiosum, and T ‐cell dysfunction
ConclusionsWe report a novel primary immunodeficiency, and a differential molecular diagnosis to CXCR4‐, DOCK8‐, GATA2‐, MAGT1‐, MCM4‐, STK4‐, RHOH‐, TMC6‐, and TMC8‐related diseases. The specific variant may represent a Norwegian founder variant segregating on a population‐specific haplotype. A likely Norwegian founder variant was detected by exome sequencing in four patients from three different families. The patients had signs of primary immunodeficiency and common skin phenotype of warts, molluscs, and dermatitis since early childhood. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - September 1, 2016 Category: Genetics & Stem Cells Authors: Hanne S. Sorte, Liv T. Osnes, B ørre Fevang, Pål Aukrust, Hans C. Erichsen, Paul H. Backe, Tore G. Abrahamsen, Ole B. Kittang, Torstein Øverland, Shalini N. Jhangiani, Donna M. Muzny, Magnus D. Vigeland, Pubudu Samarakoon, Tomasz Gambin, Zeynep H. C. A Tags: Original Article Source Type: research

Issue Information
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - September 1, 2016 Category: Genetics & Stem Cells Tags: Issue Information Source Type: research

Pitfalls in genetic testing: the story of missed SCN1A mutations
ConclusionWe illustrate the pitfalls of Sanger sequencing and most importantly provide evidence thatSCN1A mutations are an even more frequent cause of DS than already anticipated. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - July 18, 2016 Category: Genetics & Stem Cells Authors: Tania Dj émié, Sarah Weckhuysen, Sarah Spiczak, Gemma L. Carvill, Johanna Jaehn, Anna‐Kaisa Anttonen, Eva Brilstra, Hande S. Caglayan, Carolien G. Kovel, Christel Depienne, Eija Gaily, Elena Gennaro, Beatriz G. Giraldez, Padhraig Gormley, Tags: Original Article Source Type: research

A view on clinical genetics and genomics in Spain: of challenges and opportunities
. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - July 18, 2016 Category: Genetics & Stem Cells Authors: Teresa Pàmpols, Feliciano J. Ramos, Pablo Lapunzina, Ignasi Gozalo‐Salellas, Luis A. Pérez‐Jurado, Aurora Pujol Tags: Genetics and Genomic Medicine around the World Source Type: research

Lessons learned from the search for genes responsible for rare Mendelian disorders
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - July 18, 2016 Category: Genetics & Stem Cells Authors: Nara L. Sobreira, David Valle Tags: Invited Commentary Source Type: research

Issue Information
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - July 18, 2016 Category: Genetics & Stem Cells Tags: Issue Information Source Type: research

A novel de novo TBX5 mutation in a patient with Holt –Oram syndrome leading to a dramatically reduced biological function
ConclusionThese results suggest that the dramatic functional alteration of the p.Pro85Thr mutation leads to the distinctive phenotype of the patient. We have identified a so far unpublished TBX5 mutation which occurs de novo in the patient diagnosed for HOS with healthy parents. The mutation is located in a highly conserved region of TBX5 and is predicted to be damaging. Functional experiments confirmed a dramatically reduced biological activity of the mutated TBX5 protein. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - July 14, 2016 Category: Genetics & Stem Cells Authors: Martina Dre ßen, Harald Lahm, Armin Lahm, Klaudia Wolf, Stefanie Doppler, Marcus‐André Deutsch, Julie Cleuziou, Jelena Pabst von Ohain, Patric Schön, Peter Ewert, Ivan Malcic, Rüdiger Lange, Markus Krane Tags: Original Article Source Type: research

A novel de novo TBX5 mutation in a patient with Holt–Oram syndrome leading to a dramatically reduced biological function
ConclusionThese results suggest that the dramatic functional alteration of the p.Pro85Thr mutation leads to the distinctive phenotype of the patient. We have identified a so far unpublished TBX5 mutation which occurs de novo in the patient diagnosed for HOS with healthy parents. The mutation is located in a highly conserved region of TBX5 and is predicted to be damaging. Functional experiments confirmed a dramatically reduced biological activity of the mutated TBX5 protein. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - July 14, 2016 Category: Genetics & Stem Cells Authors: Martina Dreßen, Harald Lahm, Armin Lahm, Klaudia Wolf, Stefanie Doppler, Marcus‐André Deutsch, Julie Cleuziou, Jelena Pabst von Ohain, Patric Schön, Peter Ewert, Ivan Malcic, Rüdiger Lange, Markus Krane Tags: Original Article Source Type: research

Mentors without Borders
is a proposed international mentoring network that allows trainee geneticists to identify mentors from a list of volunteers who are not at one's own institution. It is an experiment, a matchmaker between a junior and a senior professional. These mentors do not replace the mentors at the home institution but allow the mentee, if desired, to identify mentors outside of their own institution. We envision that different ways of communicating and/or different mentor‐mentee relationships may prove beneficial to the trainee and the mentor. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - July 1, 2016 Category: Genetics & Stem Cells Authors: Maximilian Muenke Tags: Invited Commentary Source Type: research

Targeted sequencing of 351 candidate genes for epileptic encephalopathy in a large cohort of patients
ConclusionMutations in genes described in OMIM as, for example, intellectual disability gene can lead to phenotypes that get classified as EE in the clinic. We confirmed existing literature reports that de novo loss‐of‐function HNRNPUmutations lead to severe developmental delay and febrile seizures in the first year of life. Genes that were previously reported to have been found mutated in patients with epileptic encephalopathy were tested in a new patient cohort. Probably pathogenic variants were found in known genes for epileptic encephalopathy and in genes for intellectual disability syndromes. A de novo variant in...
Source: Molecular Genetics & Genomic Medicine - July 1, 2016 Category: Genetics & Stem Cells Authors: Carolien G.F. Kovel, Eva H. Brilstra, Marjan J.A. Kempen, Ruben Slot, Isaac J. Nijman, Zaid Afawi, Peter De Jonghe, Tania Dj émié, Renzo Guerrini, Katia Hardies, Ingo Helbig, Rik Hendrickx, Moine Kanaan, Uri Kramer, Anna‐Elina E. Lehesjoki, Johannes R Tags: Original Article Source Type: research

ADGRL3 (LPHN3) variants are associated with a refined phenotype of ADHD in the MTA study
ConclusionThe detection of susceptibility conferred by ADGRL3 variants in the extreme phenotype of continued diagnosis of ADHD‐C from childhood to adolescence provides additional support that the association of ADGRL3 and ADHD is not spurious. Exploring genetic effects in longitudinal cohorts, in which refined, age‐dependent phenotypes are documented, is crucial to understand the natural history of ADHD. ADGRL3 (LPHN3) variants are associated with ADHD susceptibility in cross‐sectional studies and in longitudinal studies. Evidence from a large longitudinal study is present in this publication. (Source: Molecular Gen...
Source: Molecular Genetics & Genomic Medicine - July 1, 2016 Category: Genetics & Stem Cells Authors: Maria T. Acosta, James Swanson, Annamarie Stehli, Brooke S. G. Molina, , Ariel F. Martinez, Mauricio Arcos‐Burgos, Maximilian Muenke Tags: Original Article Source Type: research

Population ‐specific single‐nucleotide polymorphism confers increased risk of venous thromboembolism in African Americans
ConclusionsWe found a variant, PROS1 V510M, in an African American family with VTE and clinical laboratory abnormalities in Protein S. Additionally, we found that this variant conferred increased risk of VTE in a case–control study of African Americans. In the ESP cohort, the variant is nearly absent in ESP European descent subjects (n = 3, allele frequency: 0.03%). Additionally, in 1000 Genomes Phase 3 data, the variant only appears in African descent populations. Thus, PROS1 V510M is a population‐specific genetic risk factor for VTE in African Americans. We identified a novel association between a muta...
Source: Molecular Genetics & Genomic Medicine - June 21, 2016 Category: Genetics & Stem Cells Authors: Roxana Daneshjou, Larisa H. Cavallari, Peter E. Weeke, Konrad J. Karczewski, Katarzyna Drozda, Minoli A. Perera, Julie A. Johnson, Teri E. Klein, Carlos D. Bustamante, Dan M. Roden, Christian Shaffer, Joshua C. Denny, James L. Zehnder, Russ B. Altman Tags: Original Article Source Type: research

Erratum
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - May 12, 2016 Category: Genetics & Stem Cells Authors: Josephine Wincent, Aron Luthman, Martine Belzen, Christian Lans, Johanna Albert, Ann Nordgren, Britt‐Marie Anderlid Tags: Erratum Source Type: research

Medical genetics and genomic medicine in the Dominican Republic: challenges and opportunities
. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - May 12, 2016 Category: Genetics & Stem Cells Authors: Juvianee I. Estrada‐Veras, Giselle A. Cabrera‐Peña, Ceila Pérez‐Estrella de Ferrán Tags: Genetics and Genomic Medicine around the World Source Type: research

Clinical care models in the era of next‐generation sequencing
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - May 12, 2016 Category: Genetics & Stem Cells Authors: Anne Slavotinek Tags: Invited Commentary Source Type: research

Issue Information
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - May 12, 2016 Category: Genetics & Stem Cells Tags: Issue Information Source Type: research

Concordance between whole ‐exome sequencing and clinical Sanger sequencing: implications for patient care
We report high concordance for well‐covered coding variants, supporting the use of WES as a screening tool for heterogeneous disorders, and recommend the use of supplementary Sanger sequencing for poorly‐covered genes when the clinical suspicion is high. Importantly, despite remaining difficulties with achieving complete coverage of the whole exome, 10 (38.5%) of the 26 compared patients were diagnosed through WES. The direct comparison of 391 coding and intronic variants identified by clinical Sanger sequencing to the whole‐exome sequencing (WES) results of 26 previously undiagnosed patients identified high concord...
Source: Molecular Genetics & Genomic Medicine - May 10, 2016 Category: Genetics & Stem Cells Authors: Alison Hamilton, Martine T étreault, David A. Dyment, Ruobing Zou, Kristin Kernohan, Michael T. Geraghty, , , Taila Hartley, Kym M. Boycott Tags: Original Article Source Type: research

The prevalence and distribution of the amyloidogenic transthyretin (TTR) V122I allele in Africa
ConclusionsOur data are consistent with a small number of founder carriers of the amyloidogenic TTR V122I (p.Val142Ile) allele in southern West Africa, with no apparent advantage or disadvantage of an allele carrying newborn reaching adulthood. In U.S. African Americans, the allele represents a significant risk for congestive heart failure late in life. If clinical penetrance is similar in African countries with high allele frequencies, then cardiac amyloidosis could also represent a significant cause of heart disease in the elderly in those populations. The substitution of isoleucine for valine at position 122 in the hum...
Source: Molecular Genetics & Genomic Medicine - May 1, 2016 Category: Genetics & Stem Cells Authors: Daniel R. Jacobson, Alice A. Alexander, Clement Tagoe, W. T. Garvey, Scott M. Williams, Sara Tishkoff, David Modiano, Sodiomon B. Sirima, Issa Kalidi, Amadou Toure, Joel N. Buxbaum Tags: Original Article Source Type: research

Usher syndrome in Denmark: mutation spectrum and some clinical observations
ConclusionMutations that lead to USH1 were predominantly identified in MYO7A (75%), whereas all mutations in USH2 cases were identified in USH2A. The MYO7A mutation c.93C>A, p.(Cys31*) accounted for 33% of all USH1 mutations and the USH2A c.2299delG, p.(Glu767Serfs*21) variant accounted for 45% of all USH2 mutations in the Danish cohort. We combined new mutation data in Usher syndrome (USH) with previously published. In total, we present a comprehensive overview of mutations identified in 100 patients wiith USH from Denmark. The Myo7a mutation p.Cys31* accounted for 33% of all USH1 mutations and the USH2A mutation p.Gl...
Source: Molecular Genetics & Genomic Medicine - May 1, 2016 Category: Genetics & Stem Cells Authors: Shzeena Dad, Nanna Dahl Rendtorff, Lisbeth Tranebjærg, Karen Grønskov, Helena Gásdal Karstensen, Vigdis Brox, Øivind Nilssen, Anne‐Françoise Roux, Thomas Rosenberg, Hanne Jensen, Lisbeth Birk Møller Tags: Original Article Source Type: research

Population‐specific single‐nucleotide polymorphism confers increased risk of venous thromboembolism in African Americans
ConclusionsWe found a variant, PROS1 V510M, in an African American family with VTE and clinical laboratory abnormalities in Protein S. Additionally, we found that this variant conferred increased risk of VTE in a case–control study of African Americans. In the ESP cohort, the variant is nearly absent in ESP European descent subjects (n = 3, allele frequency: 0.03%). Additionally, in 1000 Genomes Phase 3 data, the variant only appears in African descent populations. Thus, PROS1 V510M is a population‐specific genetic risk factor for VTE in African Americans. We identified a novel association between a muta...
Source: Molecular Genetics & Genomic Medicine - May 1, 2016 Category: Genetics & Stem Cells Authors: Roxana Daneshjou, Larisa H. Cavallari, Peter E. Weeke, Konrad J. Karczewski, Katarzyna Drozda, Minoli A. Perera, Julie A. Johnson, Teri E. Klein, Carlos D. Bustamante, Dan M. Roden, Christian Shaffer, Joshua C. Denny, James L. Zehnder, Russ B. Altman Tags: Original Article Source Type: research

The effect of parental age on the presence of de novo mutations – Lessons from neurofibromatosis type I
Abstract BackgroundNeurofibromatosis type 1 (NF1) is the most common autosomal dominant neurocutaneous disease with a prevalence of 1:2500. Approximately, 50% of the cases are sporadic. Advanced paternal age is associated with germline mutations and autosomal diseases. We aimed to use NF1 as a paradigm to study the effect of parental age on sporadic mutation rates for both advanced and younger parental ages. MethodsThe medical charts of 118 NF1 pediatric patients followed in a specialized Israeli NF1 clinic were evaluated. Thirty‐one cases were diagnosed by genetic tests and 87 by NIH clinical criteria. Sixty‐four case...
Source: Molecular Genetics & Genomic Medicine - May 1, 2016 Category: Genetics & Stem Cells Authors: Tom Dubov, Hagit Toledano‐Alhadef, Felix Bokstein, Shlomi Constantini, Shay Ben‐Shachar Tags: Original Article Source Type: research

Founder mutation in KCNJ10 in Pakistani patients with EAST syndrome
ConclusionBy knowing the prevalent mutation in a given population more efficient diagnostics can be performed and the families can benefit from specific counseling. Providing genetic evidence for a founder mutation in a rare kidney, brain, and inner ear disease in a Pakistani population. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - May 1, 2016 Category: Genetics & Stem Cells Authors: Ola Abdelhadi, Daniela Iancu, Mehmet Tekman, Horia Stanescu, Detlef Bockenhauer, Robert Kleta Tags: Original Article Source Type: research

A 2.5 ‐year snapshot of Mendelian discovery
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - April 3, 2016 Category: Genetics & Stem Cells Authors: Benjamin D. Solomon, Teresa Lee, Anh ‐Dao Nguyen, Tyra G. Wolfsberg Tags: Editorial Source Type: research

Novel de novo EEF1A2 missense mutations causing epilepsy and intellectual disability
ConclusionsEEF1A2 should be considered as a causative gene not only in cases of epileptic encephalopathy but also in children with less severe epilepsy and intellectual disability. The emergence of a possible discernible phenotype, a broad nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth may help in identifying patients with mutations in EEF1A2. Exome sequencing has led to the discovery of mutations in novel causative genes for epilepsy. One such gene is EEF1A2, which has been found to be mutated de novo in five cases of severe epilepsy. We now report on a further seven cases, each wit...
Source: Molecular Genetics & Genomic Medicine - April 3, 2016 Category: Genetics & Stem Cells Authors: Wayne W.K. Lam, John J. Millichap, Dinesh C. Soares, Richard Chin, Ailsa McLellan, David R. FitzPatrick, Frances Elmslie, Melissa M. Lees, G. Bradley Schaefer, , Catherine M. Abbott Tags: Original Article Source Type: research

GATA5 mutation homozygosity linked to a double outlet right ventricle phenotype in a Lebanese patient
ConclusionOur results do prove that p.Y142H is associated with DORV and suggests includingGATA5 as a potential gene to be screened in patients with this phenotype. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - March 17, 2016 Category: Genetics & Stem Cells Authors: Kameel Kassab, Hadla Hariri, Lara Gharibeh, Akl C. Fahed, Manal Zein, Inaam El ‐Rassy, Mona Nemer, Issam El‐Rassi, Fadi Bitar, Georges Nemer Tags: Original Article Source Type: research

Genetics and genomic medicine in Mali: challenges and future perspectives
. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - March 17, 2016 Category: Genetics & Stem Cells Authors: Guida Landouré, Oumar Samassékou, Mahamadou Traoré, Katherine G. Meilleur, Cheick Oumar Guinto, Barrington G. Burnett, Charlotte J. Sumner, Kenneth H. Fischbeck Tags: Genetics and Genomic Medicine around the World Source Type: research

Invited commentary: The need for human genetics and genomics in dental school curricula
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - March 17, 2016 Category: Genetics & Stem Cells Authors: P. Suzanne Hart, Thomas C. Hart Tags: Invited Commentary Source Type: research

Issue Information
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - March 17, 2016 Category: Genetics & Stem Cells Tags: Issue Information Source Type: research

Computational assessment of feature combinations for pathogenic variant prediction
ConclusionExisting pathogenicity prediction methods can be further improved. We investigated which combination of existing methods, variant features, and gene features archived the best performance in the prediction of pathogenic variants. We found that combining the number of “biological process” Gene Ontology annotations of a gene with the methods PON‐P2 and PROVEAN significantly improved prediction of pathogenic variants, outperforming all individual methods. Analysis of the Gene Ontology feature suggests that it is not a variant‐dependent annotation bias but reflects the multifunctional nature of disea...
Source: Molecular Genetics & Genomic Medicine - March 14, 2016 Category: Genetics & Stem Cells Authors: Eva König, Johannes Rainer, Francisco S. Domingues Tags: Original Article Source Type: research

Importance of nonsynonymous OCA2 variants in human eye color prediction
ConclusionOur data showed that rs74653330:A>T (p.Ala481Thr) and rs121918166:G>A (p.Val443Ile) have a measurable effect on normal pigmentation variation. We showed that the two variants, rs7465330 and rs129119166 had a measurable effect on eye color variation. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - March 11, 2016 Category: Genetics & Stem Cells Authors: Jeppe D. Andersen, Carlotta Pietroni, Peter Johansen, Mikkel M. Andersen, Vania Pereira, Claus Børsting, Niels Morling Tags: Original Article Source Type: research

The limitations of qPCR telomere length measurement in diagnosing dyskeratosis congenita
Abstract BackgroundTelomere length
Source: Molecular Genetics & Genomic Medicine - March 1, 2016 Category: Genetics & Stem Cells Authors: Shahinaz M. Gadalla, Payal P. Khincha, Hormuzd A. Katki, Neelam Giri, Jason Y. Y. Wong, Stephen Spellman, Jack A. Yanovski, Joan C. Han, Immaculata De Vivo, Blanche P. Alter, Sharon A. Savage Tags: Original Article Source Type: research

Concordance between whole‐exome sequencing and clinical Sanger sequencing: implications for patient care
We report high concordance for well‐covered coding variants, supporting the use of WES as a screening tool for heterogeneous disorders, and recommend the use of supplementary Sanger sequencing for poorly‐covered genes when the clinical suspicion is high. Importantly, despite remaining difficulties with achieving complete coverage of the whole exome, 10 (38.5%) of the 26 compared patients were diagnosed through WES. The direct comparison of 391 coding and intronic variants identified by clinical Sanger sequencing to the whole‐exome sequencing (WES) results of 26 previously undiagnosed patients identified high concord...
Source: Molecular Genetics & Genomic Medicine - March 1, 2016 Category: Genetics & Stem Cells Authors: Alison Hamilton, Martine Tétreault, David A. Dyment, Ruobing Zou, Kristin Kernohan, Michael T. Geraghty, , , Taila Hartley, Kym M. Boycott Tags: Original Article Source Type: research

Pitfalls in genetic testing: the story of missed SCN1A mutations
ConclusionWe illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A mutations are an even more frequent cause of DS than already anticipated. We explored to what extent inconsistencies between Sanger sequencing and next‐generation sequencing affect the molecular diagnosis of patients. Hereto we focused on the analysis of mutations in SCN1A, the major gene implicated in Dravet syndrome and epilepsy. We illustrate the pitfalls of genetic screening technologies and most importantly provide evidence that SCN1A mutations are an even more frequent cause of Dravet syndrome than already an...
Source: Molecular Genetics & Genomic Medicine - March 1, 2016 Category: Genetics & Stem Cells Authors: Tania Djémié, Sarah Weckhuysen, Sarah Spiczak, Gemma L. Carvill, Johanna Jaehn, Anna‐Kaisa Anttonen, Eva Brilstra, Hande S. Caglayan, Carolien G. Kovel, Christel Depienne, Eija Gaily, Elena Gennaro, Beatriz G. Giraldez, Padhraig Gormley, Rosa Guerrero Tags: Original Article Source Type: research

A 2.5‐year snapshot of Mendelian discovery
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - March 1, 2016 Category: Genetics & Stem Cells Authors: Benjamin D. Solomon, Teresa Lee, Anh‐Dao Nguyen, Tyra G. Wolfsberg Tags: Editorial Source Type: research

Analysis of a large choroideremia dataset does not suggest a preference for inclusion of certain genotypes in future trials of gene therapy
ConclusionThere is no evidence to support exclusion of CHM patients from clinical trials based on their genotypes or any potential genotype–phenotype correlations. Choroideremia is an X‐linked inherited retinal degeneration that causes nyctalopia, progressive loss of visual fields leading to loss of central visual acuity. This natural history study describes the onset and progression of these factors with respect to age and causative mutation in the CHM gene. No genotype–phenotype correlations existed within this study suggesting all genotypes could be included in future clinical trials of gene therapy in ch...
Source: Molecular Genetics & Genomic Medicine - February 28, 2016 Category: Genetics & Stem Cells Authors: Paul R. Freund, Yuri V. Sergeev, Ian M. MacDonald Tags: Original Article Source Type: research

A novel approach for next ‐generation sequencing of circulating tumor cells
ConclusionThese spiking experiments provide proof of concept of a clinically applicable workflow for real‐time monitoring of patient tumor using noninvasive liquid biopsies. The application of solid tumor next‐generation sequencing (NGS) approaches to circulating tumor samples has been hampered by the low‐input DNA available from rare circulating tumor cells (CTCs), and whole genome amplification (WGA) approaches used to generate sufficient input DNA are often incompatible with blood collection tube preservatives used to facilitate clinical sample batching. We developed a novel approach combining tumor cell isolatio...
Source: Molecular Genetics & Genomic Medicine - February 28, 2016 Category: Genetics & Stem Cells Authors: Stephanie S. Yee, David B. Lieberman, Tatiana Blanchard, JulieAnn Rader, Jianhua Zhao, Andrea B. Troxel, Daniel DeSloover, Alan J. Fox, Robert D. Daber, Bijal Kakrecha, Shrey Sukhadia, George K. Belka, Angela M. DeMichele, Lewis A. Chodosh, Jennifer J. D. Tags: Method Source Type: research

Mosaic ratio quantification of isochromosome 12p in Pallister–Killian syndrome using droplet digital PCR
ConclusionDroplet digital PCR should be considered as an effective tool for both clinical and research analytics to precisely quantify mosaic genomic copy number alterations or mosaic mutations. We report the utility of the droplet digital PCR system in quantifying the mosaic ratio of isochromosome 12p in Pallister–Killian syndrome. Droplet digital PCR should be considered as an effective tool for both clinical and research analytics to precisely quantify mosaic genomic copy number alterations or mosaic mutations. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - January 20, 2016 Category: Genetics & Stem Cells Authors: Katsunori Fujiki, Katsuhiko Shirahige, Maninder Kaur, Matthew A. Deardorff, Laura K. Conlin, Ian D. Krantz, Kosuke Izumi Tags: Original Article Source Type: research

Development of a diagnostic DNA chip to screen for 30 autosomal recessive disorders in the Hutterite population
ConclusionsOur analysis indicates that the chip is a sensitive and specific means of carrier testing in the Hutterite population and can serve as a model for other founder populations. Hutterites, a religious isolate located in North America, have a number of genetic disorders that are unique and/or over‐represented. A diagnostic chip that simultaneously tests for 30 autosomal recessive disorders of significance to this population was developed and validated in partnership with Asper Biotech. We have determined that this diagnostic chip provides a sensitive and specific means for carrier testing and has the potential to...
Source: Molecular Genetics & Genomic Medicine - January 19, 2016 Category: Genetics & Stem Cells Authors: Barbara Triggs‐Raine, Tamara Dyck, Kym M. Boycott, A. Micheil Innes, Carole Ober, Jillian S. Parboosingh, Alexis Botkin, Cheryl R. Greenberg, Elizabeth L. Spriggs Tags: Original Article Source Type: research

Panel testing reveals nonsense and missense CDH1 mutations in families without hereditary diffuse gastric cancer
ConclusionsOur study demonstrates the need for further analysis of CDH1 mutation penetrance in order to better counsel asymptomatic CDH1 mutation carriers on preventative measures and general care. Here, we present two families with pathogenic CDH1 mutations. The first family carries a novel truncating, nonsense CDH1 mutation that we were able to trace for three generations, but reports no family history of diffuse gastric cancer. The occurrence of cancer in this family deviates significantly from the expectation for hereditary diffuse gastric cancer. The proband from the second family presents with breast cancer and carr...
Source: Molecular Genetics & Genomic Medicine - January 13, 2016 Category: Genetics & Stem Cells Authors: Julie M. Huynh, Christina M. Laukaitis Tags: Clinical Report Source Type: research

Johann Gregor Mendel: paragon of experimental science
This is a foreword on the life and work of one of the greatest minds of the 20th century, the father of modern genetics, Johann Gregor Mendel. (Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - January 8, 2016 Category: Genetics & Stem Cells Authors: Mauricio De Castro Tags: Invited Commentary Source Type: research

Issue Information
(Source: Molecular Genetics & Genomic Medicine)
Source: Molecular Genetics & Genomic Medicine - January 8, 2016 Category: Genetics & Stem Cells Tags: Issue Information Source Type: research