American Journal of Medical Genetics Part C: Seminars in Medical Genetics This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Phenotype and genotype in Nicolaides–Baraitser syndrome
Nicolaides–Baraitser syndrome (NCBRS) is an intellectual disability (ID)/multiple congenital anomalies syndrome caused by non‐truncating mutations in the ATPase region of SMARCA2, which codes for one of the two alternative catalytic subunits of the BAF chromatin remodeling complex. We analyzed 61 molecularly confirmed cases, including all previously reported patients (n = 47) and 14 additional unpublished individuals. NCBRS is clinically and genetically homogeneous. The cardinal features (ID, short stature, microcephaly, typical face, sparse hair, brachydactyly, prominent interphalangeal joints, behavioral problems...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - August 28, 2014 Category: Genetics & Stem Cells Authors: Sérgio B. Sousa, Raoul C. Hennekam, Tags: Research Article Source Type: research

SWI/SNF chromatin remodeling complexes and cancer
The identification of mutations and deletions in the SMARCB1 locus in chromosome band 22q11.2 in pediatric rhabdoid tumors provided the first evidence for the involvement of the SWI/SNF chromatin remodeling complex in cancer. Over the last 15 years, alterations in more than 20 members of the complex have been reported in a variety of human tumors. These include germline mutations and copy number alterations in SMARCB1, SMARCA4, SMARCE1, and PBRM1 that predispose carriers to both benign and malignant neoplasms. Somatic mutations, structural abnormalities, or epigenetic modifications that lead to reduced or aberrant expressi...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - August 28, 2014 Category: Genetics & Stem Cells Authors: Jaclyn A. Biegel, Tracy M. Busse, Bernard E. Weissman Tags: Research Article Source Type: research

DOORS syndrome: Phenotype, genotype and comparison with Coffin‐Siris syndrome
DOORS syndrome (Deafness, Onychodystrophy, Osteodystrophy, mental Retardation, Seizures) is characterized mainly by sensorineural deafness, shortened terminal phalanges with small nails of hands and feet, intellectual deficiency, and seizures. Half of the patients with all clinical features have mutations in TBC1D24. We review here the manifestations of patients clinically diagnosed with DOORS syndrome. In this cohort of 32 families (36 patients) we detected 13 individuals from 10 families with TBC1D24 mutations. Subsequent whole exome sequencing in the cohort showed the same de novoSMARCB1 mutation (c.1130G>A), known t...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - August 28, 2014 Category: Genetics & Stem Cells Authors: Philippe M. Campeau, Raoul C. Hennekam, Tags: Research Article Source Type: research

The ARID1B Phenotype: What we have learned so far
Evidence is now accumulating from a number of sequencing studies that ARID1B not only appears to be one of the most frequently mutated intellectual disability (ID) genes, but that the range of phenotypes caused by ARID1B mutations seems to be extremely wide. Thus, it is one of the most interesting ID genes identified so far in the exome sequencing era. In this article, we review the literature surrounding ARID1B and attempt to delineate the ARID1B phenotype. The vast majority of published ARID1B patients have been ascertained through studies of Coffin–Siris syndrome (CSS), which leads to bias when documenting the frequen...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - August 28, 2014 Category: Genetics & Stem Cells Authors: Gijs W.E. Santen, Jill Clayton‐Smith, Tags: Research Article Source Type: research

Genotype‐phenotype correlation of Coffin‐Siris syndrome caused by mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A
Coffin–Siris syndrome (CSS) is a rare congenital malformation syndrome, recently found to be caused by mutations in several genes encoding components of the BAF complex. To date, 109 patients have been reported with their mutations: SMARCB1 (12%), SMARCA4 (11%), SMARCE1 (2%), ARID1A (7%), ARID1B (65%), and PHF6 (2%). We review genotype‐phenotype correlation of all previously reported patients with mutations in SMARCB1, SMARCA4, SMARCE1, and ARID1A through reassessment of their clinical and molecular findings. Cardinal features of CSS included variable degrees of intellectual disability (ID) predominantly affecting spee...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - August 28, 2014 Category: Genetics & Stem Cells Authors: Tomoki Kosho, Nobuhiko Okamoto, Tags: Research Article Source Type: research

The transcriptional regulator ADNP links the BAF (SWI/SNF) complexes with autism
Mutations in ADNP were recently identified as a frequent cause of syndromic autism, characterized by deficits in social communication and interaction and restricted, repetitive behavioral patterns. Based on its functional domains, ADNP is a presumed transcription factor. The gene interacts closely with the SWI/SNF complex by direct and experimentally verified binding of its C‐terminus to three of its core components. A detailed and systematic clinical assessment of the symptoms observed in our patients allows a detailed comparison with the symptoms observed in other SWI/SNF disorders. While the mutational mechanism of th...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - August 28, 2014 Category: Genetics & Stem Cells Authors: Geert Vandeweyer, Céline Helsmoortel, Anke Van Dijck, Anneke T. Vulto‐van Silfhout, Bradley P. Coe, Raphael Bernier, Jennifer Gerdts, Liesbeth Rooms, Jenneke van den Ende, Madhura Bakshi, Meredith Wilson, Ann Nordgren, Laura G. Hendon, Omar A. Abdulrah Tags: Research Article Source Type: research

The role of BAF (mSWI/SNF) complexes in mammalian neural development
The BAF (mammalian SWI/SNF) complexes are a family of multi‐subunit ATP‐dependent chromatin remodelers that use ATP hydrolysis to alter chromatin structure. Distinct BAF complex compositions are possible through combinatorial assembly of homologous subunit families and can serve non‐redundant functions. In mammalian neural development, developmental stage‐specific BAF assemblies are found in embryonic stem cells, neural progenitors and postmitotic neurons. In particular, the neural progenitor‐specific BAF complexes are essential for controlling the kinetics and mode of neural progenitor cell division, while neuro...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - June 1, 2014 Category: Genetics & Stem Cells Authors: Esther Y. Son, Gerald R. Crabtree Tags: Article Source Type: research

Clinical features, diagnostic criteria, and management of Coffin–Siris syndrome
Coffin–Siris syndrome (OMIM#135900) is a multiple congenital anomaly syndrome classically characterized by hypo‐ or aplasia of the fifth digit nails or phalanges, as well as coarse facial features, sparse scalp hair, and moderate to severe cognitive and/or developmental delay. The recent identification of molecular etiologies has served to effectively characterize a large set of patients who have been described with Coffin–Siris between the time of its initial description and the present. However, despite recent advances, a number of patients who traditionally fit the diagnosis have yet to have identified causes. Thi...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - June 1, 2014 Category: Genetics & Stem Cells Authors: Samantha S. Vergano, Matthew A. Deardorff Tags: Research Article Source Type: research

Females with de novo aberrations in PHF6: Clinical overlap of Borjeson–Forssman–Lehmann with Coffin–Siris syndrome
Recently, de novo aberrations in PHF6 were identified in females with intellectual disability and with a distinct phenotype including a characteristic facial gestalt with bitemporal narrowing, prominent supraorbital ridges, synophrys, a short nose and dental anomalies, tapering fingers with brachytelephalangy, clinodactyly and hypoplastic nails, short toes with hypoplastic nails, and linear skin hyperpigmentation. In adolescent or older patients, this phenotype overlaps but is not identical with Borjeson–Forssman–Lehmann syndrome in males, caused by X‐linked recessive mutations in PHF6. In younger girls there seems t...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - June 1, 2014 Category: Genetics & Stem Cells Authors: Christiane Zweier, Olaf Rittinger, Ingrid Bader, Siren Berland, Trevor Cole, Franziska Degenhardt, Nataliya Di Donato, Luitgard Graul‐Neumann, Juliane Hoyer, Sally Ann Lynch, Ingrid Vlasak, Dagmar Wieczorek Tags: Research Article Source Type: research

Numerous BAF complex genes are mutated in Coffin–Siris syndrome
Coffin–Siris syndrome (CSS; OMIM#135900) is a rare congenital anomaly syndrome characterized by intellectual disability, coarse face, hypertrichosis, and absence/hypoplasia of the fifth digits' nails. As the majority of patients are sporadic, an autosomal dominant inheritance model has been postulated. Recently, whole exome sequencing (WES) emerged as a comprehensive analytical method for rare variants. We applied WES on five CSS patients and found two de novo mutations in SMARCB1. SMARCB1 was completely sequenced in 23 CSS patients and the mutations were found in two more patients. As SMARCB1 encodes a subunit of the BA...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - June 1, 2014 Category: Genetics & Stem Cells Authors: Noriko Miyake, Yoshinori Tsurusaki, Naomichi Matsumoto Tags: Research Article Source Type: research

Polymicrogyria: A common and heterogeneous malformation of cortical development
Polymicrogyria (PMG) is one of the most common malformations of cortical development. It is characterized by overfolding of the cerebral cortex and abnormal cortical layering. It is a highly heterogeneous malformation with variable clinical and imaging features, pathological findings, and etiologies. It may occur as an isolated cortical malformation, or in association with other malformations within the brain or body as part of a multiple congenital anomaly syndrome. Polymicrogyria shows variable topographic patterns with the bilateral perisylvian pattern being most common. Schizencephaly is a subtype of PMG in which the o...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - May 28, 2014 Category: Genetics & Stem Cells Authors: Chloe A. Stutterd, Richard J. Leventer Tags: Research Article Source Type: research

Cerebellar hypoplasia: Differential diagnosis and diagnostic approach
Cerebellar hypoplasia (CH) refers to a cerebellum with a reduced volume, and is a common, but non‐specific neuroimaging finding. The etiological spectrum of CH is wide and includes both primary (malformative) and secondary (disruptive) conditions. Primary conditions include chromosomal aberrations (e.g., trisomy 13 and 18), metabolic disorders (e.g., molybdenum cofactor deficiency, Smith–Lemli–Opitz syndrome, and adenylosuccinase deficiency), genetic syndromes (e.g., Ritscher‐Schinzel, Joubert, and CHARGE syndromes), and brain malformations (primary posterior fossa malformations e.g., Dandy–Walker malformation, p...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - May 16, 2014 Category: Genetics & Stem Cells Authors: Andrea Poretti, Eugen Boltshauser, Dan Doherty Tags: Research Article Source Type: research

Implementation of genomic medicine in a health care delivery system: A value proposition?
The United States health care system is undergoing significant change and is seeking innovations in care delivery and reimbursement models that will lead to improved value for patients, providers, payers, and employers. Genomic medicine has the potential to be a disruptive innovation that if implemented intelligently can improve value. The article presents the perspective of the leaders of a large integrated healthcare delivery system regarding the decision to invest in implementation of genomic medicine. © 2014 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics)
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - March 11, 2014 Category: Genetics & Stem Cells Authors: Joanne E. Wade, David H. Ledbetter, Marc S. Williams Tags: Commentary Source Type: research

Leading the way to genomic medicine
The National Human Genome Research Institute, in close collaboration with its research community, is pursuing an ambitious research agenda to facilitate and promote the implementation of genomics in clinical care. Since 2011, research programs utilizing next‐generation sequencing in the management of cancer and other multigenic conditions, workup of undiagnosed conditions, and evaluation of disorders of the newborn period have been initiated, along with projects identifying clinically actionable variants and exploring the ethical and social implications of reporting these findings. Several genomic medicine symposia and o...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - March 11, 2014 Category: Genetics & Stem Cells Authors: Teri A. Manolio, Eric D. Green Tags: Invited Comment Source Type: research

Clinical pharmacogenetics implementation: Approaches, successes, and challenges
Current challenges exist to widespread clinical implementation of genomic medicine and pharmacogenetics. The University of Florida (UF) Health Personalized Medicine Program (PMP) is a pharmacist‐led, multidisciplinary initiative created in 2011 within the UF Clinical Translational Science Institute. Initial efforts focused on pharmacogenetics, with long‐term goals to include expansion to disease‐risk prediction and disease stratification. Herein we describe the processes for development of the program, the challenges that were encountered and the clinical acceptance by clinicians of the genomic medicine implementatio...
Source: American Journal of Medical Genetics Part C: Seminars in Medical Genetics - March 10, 2014 Category: Genetics & Stem Cells Authors: Kristin W. Weitzel, Amanda R. Elsey, Taimour Y. Langaee, Benjamin Burkley, David R. Nessl, Aniwaa Owusu Obeng, Benjamin J. Staley, Hui‐Jia Dong, Robert W. Allan, J. Felix Liu, Rhonda M. Cooper‐DeHoff, R. David Anderson, Michael Conlon, Michael J. Clar Tags: Research Article Source Type: research