Publications by authors named "Philip F Giampietro"

74 Publications

50 Years Ago in TheJournalofPediatrics: Understanding the Molecular Basis of 11p13 Deletion.

J Pediatr 2021 Mar;230:61

Division of Medical Genetics, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2020.10.048DOI Listing
March 2021

50 Years Ago in TheJournalofPediatrics: 50 Years Ago Today: The Expanding Phenotype of Larsen Syndrome.

J Pediatr 2021 Feb;229:94

Division of Medical Genetics, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2020.08.075DOI Listing
February 2021

A dyadic approach to the delineation of diagnostic entities in clinical genomics.

Am J Hum Genet 2021 01;108(1):8-15

Section of Genetics and Metabolism, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.

The delineation of disease entities is complex, yet recent advances in the molecular characterization of diseases provide opportunities to designate diseases in a biologically valid manner. Here, we have formalized an approach to the delineation of Mendelian genetic disorders that encompasses two distinct but inter-related concepts: (1) the gene that is mutated and (2) the phenotypic descriptor, preferably a recognizably distinct phenotype. We assert that only by a combinatorial or dyadic approach taking both of these attributes into account can a unitary, distinct genetic disorder be designated. We propose that all Mendelian disorders should be designated as "GENE-related phenotype descriptor" (e.g., "CFTR-related cystic fibrosis"). This approach to delineating and naming disorders reconciles the complexity of gene-to-phenotype relationships in a simple and clear manner yet communicates the complexity and nuance of these relationships.
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http://dx.doi.org/10.1016/j.ajhg.2020.11.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820621PMC
January 2021

50 Years Ago in TheJournalofPediatrics: An Update on the Phenotypic Map of 18q Deletions.

J Pediatr 2021 01;228:227

Division of Medical Genetics, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2020.07.070DOI Listing
January 2021

Heterozygous loss of WBP11 function causes multiple congenital defects in humans and mice.

Hum Mol Genet 2021 Jan;29(22):3662-3678

Development & Stem Cell Biology Division, Victor Chang Cardiac Research Institute, Sydney 2010, Australia.

The genetic causes of multiple congenital anomalies are incompletely understood. Here, we report novel heterozygous predicted loss-of-function (LoF) and predicted damaging missense variants in the WW domain binding protein 11 (WBP11) gene in seven unrelated families with a variety of overlapping congenital malformations, including cardiac, vertebral, tracheo-esophageal, renal and limb defects. WBP11 encodes a component of the spliceosome with the ability to activate pre-messenger RNA splicing. We generated a Wbp11 null allele in mouse using CRISPR-Cas9 targeting. Wbp11 homozygous null embryos die prior to E8.5, indicating that Wbp11 is essential for development. Fewer Wbp11 heterozygous null mice are found than expected due to embryonic and postnatal death. Importantly, Wbp11 heterozygous null mice are small and exhibit defects in axial skeleton, kidneys and esophagus, similar to the affected individuals, supporting the role of WBP11 haploinsufficiency in the development of congenital malformations in humans. LoF WBP11 variants should be considered as a possible cause of VACTERL association as well as isolated Klippel-Feil syndrome, renal agenesis or esophageal atresia.
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http://dx.doi.org/10.1093/hmg/ddaa258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823106PMC
January 2021

Social Media Use Among Young Adults With Connective Tissue Disorders: Cross-Sectional Pilot Study.

JMIR Pediatr Parent 2020 Oct 30;3(2):e16367. Epub 2020 Oct 30.

Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, United States.

Background: Young people with genetic conditions often face challenges coping with their health condition. It can be difficult for them to meet someone with a similar condition, which is important for reinforcement of chronic illness management recommendations. Social media is used by 97% of young people in the United States and may provide those with these disorders a space for emotional expression and support. However, there is a scarcity of literature related to the use of social media among adolescents with genetic conditions as an indicator of their perception regarding their own condition.

Objective: The purpose of this pilot study was to obtain preliminary data to assess and understand social media use by young people with connective tissue disorders and determine whether they use social media to connect with patients with similar conditions or whether they would be interested in doing so.

Methods: We undertook a pilot study of selected connective tissue disorders occurring in young people between the ages of 11 and 25 years, including Marfan syndrome; Ehlers-Danlos syndrome subtypes classical, classical-like, cardiac-valvular, and vascular; Beals congenital contractual arachnodactyly; and Alport hereditary nephritis. The study took place within one pediatric clinical system. Patients were identified through electronic medical record search and International Classification of Diseases, Ninth Revision, coding at a Midwest university-based clinical system. Study subjects completed a short survey describing their experiences with their connective tissue disorders, their means of self-expression, their existing network of persons to communicate with, and their use of social media. Data analysis included nominal and bivariate regressions to compare social media use in relation to age.

Results: Our 31 participants (42% response rate) were 55% female (17/31) and their average age was 18 years (SD 5). All participants used social media and there were no statistically significant differences between social media use and age. The majority of participants (25/30, 83%) reported that they never used social media to discuss their condition (P=.09), and only 17% (5/30) knew someone online with a similar condition (P=.50). Most participants (19/30, 63%) said they would communicate with someone with a similar disorder (P=.64).

Conclusions: We found that young individuals with connective tissue disorders use at least one type of social media. A majority did not use social media to discuss their condition or know someone online with a similar condition. However, many persons were interested in finding others similarly affected. Social media could serve as a platform for young people with connective tissue disorders to connect. Peer support is important in disease management and adolescent development. Future studies should aim at understanding social media use among young people with connective tissue disorders and helping them connect with other people who have similar conditions.
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http://dx.doi.org/10.2196/16367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665944PMC
October 2020

50 Years Ago in The Journal of Pediatrics: Tolubtamide-Mediated Dysregulation of Apoptosis.

J Pediatr 2020 09;224:71

Division of Medical Genetics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2020.02.045DOI Listing
September 2020

50 Years Ago in TheJournalofPediatrics: Clinical and Genetic Delineation of Saethre-Chotzen Syndrome.

J Pediatr 2020 08;223:107

Division of Medical Genetics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2020.02.012DOI Listing
August 2020

50 Years Ago in TheJournalofPediatrics: Spectrum of GLI3 Mutations.

J Pediatr 2020 07;222:27

Division of Pediatric Genetics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2019.12.042DOI Listing
July 2020

50 Years Ago in The Journal of Pediatrics: Hand-Foot-Genital Syndrome and Its Multiple Genetic Mechanisms.

J Pediatr 2020 07;222:185

Division of Medical Genetics, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2020.01.038DOI Listing
July 2020

50 Years Ago in TheJournalofPediatrics: Understanding the Genetic Basis of Frontonasal Dysplasia.

J Pediatr 2020 06;221:80

Division of Pediatric Genetics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2019.12.014DOI Listing
June 2020

KIAA1217: A novel candidate gene associated with isolated and syndromic vertebral malformations.

Am J Med Genet A 2020 07 5;182(7):1664-1672. Epub 2020 May 5.

Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.

Vertebral malformations (VMs) are caused by alterations in somitogenesis and may occur in association with other congenital anomalies. The genetic etiology of most VMs remains unknown and their identification may facilitate the development of novel therapeutic and prevention strategies. Exome sequencing was performed on both the discovery cohort of nine unrelated probands from the USA with VMs and the replication cohort from China (Deciphering Disorders Involving Scoliosis & COmorbidities study). The discovery cohort was analyzed using the PhenoDB analysis tool. Heterozygous and homozygous, rare and functional variants were selected and evaluated for their ClinVar, HGMD, OMIM, GWAS, mouse model phenotypes, and other annotations to identify the best candidates. Genes with candidate variants in three or more probands were selected. The replication cohort was analyzed by another in-house developed pipeline. We identified rare heterozygous variants in KIAA1217 in four out of nine probands in the discovery cohort and in five out of 35 probands in the replication cohort. Collectively, we identified 11 KIAA1217 rare variants in 10 probands, three of which have not been described in gnomAD and one of which is a nonsense variant. We propose that genetic variations of KIAA1217 may contribute to the etiology of VMs.
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http://dx.doi.org/10.1002/ajmg.a.61607DOI Listing
July 2020

50 Years Ago in TheJournalofPediatrics: "CatEye Syndrome" and the Unraveling of the 22q.11.2 Genomic Region.

J Pediatr 2020 04;219:88

Division of Pediatric Genetics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2019.10.005DOI Listing
April 2020

50 Years Ago in TheJournalofPediatrics: Neurofibromatosis in Childhood.

J Pediatr 2020 03;218:27

Division of Clinical Genetics, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2019.09.033DOI Listing
March 2020

50 Years Ago in TheJournalofPediatrics: Arthrogryposis Multiplex Congenita: A Clinical Investigation.

J Pediatr 2020 02;217:72

Emerita Professor of Pediatrics, University of British Columbia, Vancouver, British Columbia.

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http://dx.doi.org/10.1016/j.jpeds.2019.08.022DOI Listing
February 2020

A male infant with Xq22.2q22.3 duplication containing PLP1 and MID2.

Mol Genet Genomic Med 2020 03 17;8(3):e1078. Epub 2020 Jan 17.

Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

Background: The Xq22.2 q23 is a complex genomic region which includes the genes MID2 and PLP1 associated with FG syndrome 5 and Pelizaeus-Merzbacher disease, respectively. There is limited information regarding the clinical outcomes observed in patients with deletions within this region.

Methods: We report on a male infant with intrauterine growth retardation (IUGR) who developed head titubation and spasticity during his postnatal hospital course.

Results: Chromosome microarray revealed a 6.7 Mb interstitial duplication of Xq22.2q22.3. Fluorescence in situ hybridization showed that the patient's mother also possessed the identical duplication in the Xq22.3q22.3 region. Among the 34 OMIM genes in this interval, the duplication of the PLP1 (OMIM# 300401) and MID2 (OMIM# 300204) appears to be the most significant contributors to the patient's clinical features. Mutations and duplications of PLP1 are associated with X-linked recessive Pelizaeus-Merzbacher disease (PMD). A single case of a Xq22.3 duplication including the MID2 has been reported in boy with features of FG syndrome. However, our patient's clinical features are not consistent with the FG syndrome phenotype.

Conclusion: Our patient's clinical features appear to be influenced by the PLP1 duplication but the clinical effect of other dosage sensitive genes influencing brain development cannot be ruled out.
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http://dx.doi.org/10.1002/mgg3.1078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057127PMC
March 2020

50 Years Ago in TheJournal ofPediatrics: Cerebral Gigantism: Concentrations of Amino Acids in Plasma and Muscle.

J Pediatr 2020 01;216:43

Division of Medical Genetics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey.

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http://dx.doi.org/10.1016/j.jpeds.2019.07.036DOI Listing
January 2020

50 Years Ago in The Journal of Pediatrics: A Chromosome Survey of 2400 Normal Newborn Infants.

J Pediatr 2019 Mar;206:25

St. Christopher's Hospital for Children Department of Pediatrics Section of Clinical Genetics Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1016/j.jpeds.2018.09.001DOI Listing
March 2019

50 Years Ago in The Journal of Pediatrics: A Chromosome Survey of Unselected Live-Born Children with Congenital Abnormalities.

J Pediatr 2019 Mar;206:231

Section of Clinical Genetics St. Christopher's Hospital for Children Drexel University College of Medicine Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1016/j.jpeds.2018.09.050DOI Listing
March 2019

TBX6-associated congenital scoliosis (TACS) as a clinically distinguishable subtype of congenital scoliosis: further evidence supporting the compound inheritance and TBX6 gene dosage model.

Genet Med 2019 07 14;21(7):1548-1558. Epub 2019 Jan 14.

Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Purpose: To characterize clinically measurable endophenotypes, implicating the TBX6 compound inheritance model.

Methods: Patients with congenital scoliosis (CS) from China(N = 345, cohort 1), Japan (N = 142, cohort 2), and the United States (N = 10, cohort 3) were studied. Clinically measurable endophenotypes were compared according to the TBX6 genotypes. A mouse model for Tbx6 compound inheritance (N = 52) was investigated by micro computed tomography (micro-CT). A clinical diagnostic algorithm (TACScore) was developed to assist in clinical recognition of TBX6-associated CS (TACS).

Results: In cohort 1, TACS patients (N = 33) were significantly younger at onset than the remaining CS patients (P = 0.02), presented with one or more hemivertebrae/butterfly vertebrae (P = 4.9 × 10), and exhibited vertebral malformations involving the lower part of the spine (T8-S5, P = 4.4 × 10); observations were confirmed in two replication cohorts. Simple rib anomalies were prevalent in TACS patients (P = 3.1 × 10), while intraspinal anomalies were uncommon (P = 7.0 × 10). A clinically usable TACScore was developed with an area under the curve (AUC) of 0.9 (P = 1.6 × 10). A Tbx6 mouse model supported that a gene dosage effect underlies the TACS phenotype.

Conclusion: TACS is a clinically distinguishable entity with consistent clinically measurable endophenotypes. The type and distribution of vertebral column abnormalities in TBX6/Tbx6 compound inheritance implicate subtle perturbations in gene dosage as a cause of spine developmental birth defects responsible for about 10% of CS.
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http://dx.doi.org/10.1038/s41436-018-0377-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659397PMC
July 2019

Phenotypic heterogeneity of intellectual disability in patients with congenital insensitivity to pain with anhidrosis: A case report and literature review.

J Int Med Res 2018 Jun 5;46(6):2445-2457. Epub 2018 Apr 5.

1 Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, PR China.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive heterogeneous disorder mainly caused by mutations in the neurotrophic tyrosine receptor kinase 1 gene ( NTRK1) and characterized by insensitivity to noxious stimuli, anhidrosis, and intellectual disability. We herein report the first north Han Chinese patient with CIPA who exhibited classic phenotypic features and severe intellectual disability caused by a homozygous c.851-33T>A mutation of NTRK1, resulting in aberrant splicing and an open reading frame shift. We reviewed the literature and performed in silico analysis to determine the association between mutations and intellectual disability in patients with CIPA. We found that intellectual disability was correlated with the specific Ntrk1 protein domain that a mutation jeopardized. Mutations located peripheral to the Ntrk1 protein do not influence important functional domains and tend to cause milder symptoms without intellectual disability. Mutations that involve critical amino acids in the protein are prone to cause severe symptoms, including intellectual disability.
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http://dx.doi.org/10.1177/0300060517747164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023048PMC
June 2018

Summary of the first inaugural joint meeting of the International Consortium for scoliosis genetics and the International Consortium for vertebral anomalies and scoliosis, March 16-18, 2017, Dallas, Texas.

Am J Med Genet A 2018 01 21;176(1):253-256. Epub 2017 Nov 21.

Texas Scottish Rite Hospital for Children, Dallas, Texas.

Scoliosis represents the most common musculoskeletal disorder in children and affects approximately 3% of the world population. Scoliosis is separated into two major phenotypic classifications: congenital and idiopathic. Idiopathic scoliosis is defined as a curvature of the spine of 10° or greater visualized on plane radiograph and does not have associated vertebral malformations (VM). "Congenital" scoliosis (CS) due to malformations in vertebrae is frequently associated with other birth defects. Recently, significant advances have been made in understanding the genetic basis of both conditions. There is evidence that both conditions are etiologically related. A 2-day conference entitled "Genomic Approaches to Understanding and Treating Scoliosis" was held at Scottish Rite Hospital for Children in Dallas, Texas, to synergize research in this field. This first combined, multidisciplinary conference featured international scoliosis researchers in basic and clinical sciences. A major outcome of the conference advancing scoliosis research was the proposal and subsequent vote in favor of merging the International Consortium for Vertebral Anomalies and Scoliosis (ICVAS) and International Consortium for Scoliosis Genetics (ICSG) into a single entity called International Consortium for Spinal Genetics, Development, and Disease (ICSGDD). The ICSGDD is proposed to meet annually as a forum to synergize multidisciplinary spine deformity research.
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http://dx.doi.org/10.1002/ajmg.a.38550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525596PMC
January 2018

Prenatal presentation of Mabry syndrome with congenital diaphragmatic hernia and phenotypic overlap with Fryns syndrome.

Am J Med Genet A 2017 Oct 17;173(10):2776-2781. Epub 2017 Aug 17.

Drexel University College of Medicine, Philadelphia, Pennsylvania.

We report on a family in which initial features were compatible with Fryns syndrome. The first sibling was a stillborn female with a left diaphragmatic hernia (DH). Her clinical features overlapped with Fryns syndrome. The second pregnancy, a male fetus, was followed for polyhydramnios, hypoplastic mandible, mild enlargement of the fetal bladder, hydronephrosis, and rocker bottom foot deformities. He had facial features similar to his sibling and a large cleft of the secondary palate, small jaw, and secundum atrial septal defect. He underwent surgical repair of imperforate anus, intestinal malrotation, and placement of mucous fistula for biopsy positive Hirschsprung disease. An elevated alkaline phosphatase level of 1569 U/L was reported. Whole exome sequencing performed on the second child demonstrated compound heterozygosity for the PIGV gene with the p.A341E and p.A418D variants in trans. Hyperphosphatasia with mental retardation syndrome (HPMRS) is caused by mutations in PIGV and includes hyperphosphatasia as a diagnostic hallmark. Our patient exhibited hyperphosphatasia but without any storage material in his skin cells. His features remain similar to his sister's, but includes seizures and lacks diaphragmatic hernia. Until now, HPMRS and Fryns syndrome, despite overlapping features, were considered mutually exclusive as HPMRS involves hyperphosphatasia and Fryns typically exhibits DH. Recent identification of PIGN mutations associated with several cases of Fryns syndrome point to a common pathogenetic etiology involving inborn errors of the glycosylphosphatidylinositiol anchor biosynthetic pathway. A diagnosis of HPMRS should be considered when DH is encountered on prenatal ultrasound.
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http://dx.doi.org/10.1002/ajmg.a.38379DOI Listing
October 2017

Diaphanospondylodysostosis and ischiospinal dysostosis, evidence for one disorder with variable expression in a patient who has survived to age 9 years.

Am J Med Genet A 2017 Oct 17;173(10):2808-2813. Epub 2017 Aug 17.

Drexel University College of Medicine, Philadelphia, Pennsylvania.

Diaphanospondylodysostosis (DSD) and ischiospinal dysostosis (ISD) are both rare skeletal dysplasias consisting of abnormal axial skeletal development but normal appendicular skeletal development. Both disorders recently have been found to result from mutations in the BMPER gene. We report a patient with one deletion and one mutation of the BMPER gene who has features most consistent with DSD but who has survived to age 9 years. Survival suggests that DSD and ISD reflect a spectrum of severity of one disease process.
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http://dx.doi.org/10.1002/ajmg.a.38395DOI Listing
October 2017

Progress and perspective of TBX6 gene in congenital vertebral malformations.

Oncotarget 2016 Aug;7(35):57430-57441

Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Congenital vertebral malformation is a series of significant health problems affecting a large number of populations. It may present as an isolated condition or as a part of an underlying syndromes occurring with other malformations and/or clinical features. Disruption of the genesis of paraxial mesoderm, somites or axial bones can result in spinal deformity. In the course of somitogenesis, the segmentation clock and the wavefront are the leading factors during the entire process in which TBX6 gene plays an important role. TBX6 is a member of the T-box gene family, and its important pathogenicity in spinal deformity has been confirmed. Several TBX6 gene variants and novel pathogenic mechanisms have been recently revealed, and will likely have significant impact in understanding the genetic basis for CVM. In this review, we describe the role which TBX6 plays during human spine development including its interaction with other key elements during the process of somitogenesis. We then systematically review the association between TBX6 gene variants and CVM associated phenotypes, highlighting an important and emerging role for TBX6 and human malformations.
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http://dx.doi.org/10.18632/oncotarget.10619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302999PMC
August 2016

The genetic landscape and clinical implications of vertebral anomalies in VACTERL association.

J Med Genet 2016 07 15;53(7):431-7. Epub 2016 Apr 15.

Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Beijing, China Department of Central Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

VACTERL association is a condition comprising multisystem congenital malformations, causing severe physical disability in affected individuals. It is typically defined by the concurrence of at least three of the following component features: vertebral anomalies (V), anal atresia (A), cardiac malformations (C), tracheo-oesophageal fistula (TE), renal dysplasia (R) and limb abnormalities (L). Vertebral anomaly is one of the most important and common defects that has been reported in approximately 60-95% of all VACTERL patients. Recent breakthroughs have suggested that genetic factors play an important role in VACTERL association, especially in those with vertebral phenotypes. In this review, we summarised the genetic studies of the VACTERL association, especially focusing on the genetic aetiology of patients with vertebral anomalies. Furthermore, genetic reports of other syndromes with vertebral phenotypes overlapping with VACTERL association are also included. We aim to provide a further understanding of the genetic aetiology and a better evidence for genetic diagnosis of the association and vertebral anomalies.
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http://dx.doi.org/10.1136/jmedgenet-2015-103554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4941148PMC
July 2016

Marfan syndrome patient experiences as ascertained through postings on social media sites.

Am J Med Genet A 2015 Nov 14;167A(11):2629-34. Epub 2015 Aug 14.

Seattle Children's Research Institute, Seattle, Washington.

Marfan syndrome (MS) is a connective tissue disorder that affects thousands of adolescents [Population Reference Bureau, 2013]. Some adolescent patients with MS may use social media to express their experiences and emotions, but little is known about what patients choose to share online. To investigate social media content related to Marfan syndrome we used search terms "Marfan syndrome" and "Marfans" on six different social media sites. The top five recent and popular posts for each site were collected and coded weekly for five weeks. Posts were excluded if they were reshared content or not in English. A codebook was developed using an iterative process to categorize posts and comments. Out of 300 posts collected 147 posts (49.0%) were included for evaluation. Categories of displayed content included personal pictures, memes and pictures featuring symptoms of MS (41.5%) and personal MS experiences (27.1% of posts). One quarter of the posts specifically mentioned a positive experience or how thankful the profile owner was for their life. A unique category of posts (13.7%) referenced Austin Carlile, a celebrity singer with MS, as a role model. Physicians and healthcare providers may consider using social media to understand common MS concerns and to place future health education materials.
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http://dx.doi.org/10.1002/ajmg.a.37255DOI Listing
November 2015

SNPping away at the genetic basis of adolescent idiopathic scoliosis.

Ann Transl Med 2015 May;3(Suppl 1):S26

Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 53705, USA.

Adolescent idiopathic scoliosis (AIS) is a genetically complex disorder of spine development, defined by a lateral curvature of the spine of 10º or greater which affects children during their pubertal growth spurt. Prior linkage and candidate gene approaches to elucidating the genetic basis of AIS have been of limited use for identification of candidate genes for this condition. Genome wide association studies (GWAS) have recently identified single nucleotide polymorphisms (SNPs) in LBX1 and G protein-coupled receptor 126 (GPR126) that contribute to AIS occurrence. These discoveries support prior etiologic hypotheses regarding altered somatosensory function and skeletal growth in AIS. However, these loci account for a small percentage of the phenotypic variance associated with AIS, indicating the vast majority of the genetic causes of AIS remain to be delineated. A major translational application regarding understanding the genetic contributions to AIS relates to bracing efficacy.
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http://dx.doi.org/10.3978/j.issn.2305-5839.2015.02.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4437945PMC
May 2015

Ruptured Posterior Communicating Artery Aneurysm Associated with Aarskog Syndrome.

NMC Case Rep J 2015 Jul 20;2(3):85-87. Epub 2015 Feb 20.

Department of Neurological Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.

A 44-year-old male with Aarskog syndrome (AS) presented with subarachnoid hemorrhage secondary to ruptured posterior communicating artery aneurysm. AS, also known as faciogenital dysplasia, is an X-linked, autosomal dominant or autosomal recessive congenital developmental disorder. This syndrome is characterized by short stature in association with a variety of multiple anomalies in musculoskeletal, neurological, and urogenital systems. Cerebrovascular abnormalities such as anomalous cerebral venous drainage, dysplastic internal carotid artery, and basilar artery malformation have been reported to be associated with AS. To our knowledge this represents the first case of a ruptured intracranial aneurysm in a patient with AS.
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http://dx.doi.org/10.2176/nmccrj.2014-0022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364889PMC
July 2015

Whole exome sequencing identifies a POLRID mutation segregating in a father and two daughters with findings of Klippel-Feil and Treacher Collins syndromes.

Am J Med Genet A 2015 Jan 27;167A(1):95-102. Epub 2014 Oct 27.

University of Wisconsin-Madison, Madison, Wisconsin.

We report on a father and his two daughters diagnosed with Klippel-Feil syndrome (KFS) but with craniofacial differences (zygomatic and mandibular hypoplasia and cleft palate) and external ear abnormalities suggestive of Treacher Collins syndrome (TCS). The diagnosis of KFS was favored, given that the neck anomalies were the predominant manifestations, and that the diagnosis predated later recognition of the association between spinal segmentation abnormalities and TCS. Genetic heterogeneity and the rarity of large families with KFS have limited the ability to identify mutations by traditional methods. Whole exome sequencing identified a nonsynonymous mutation in POLR1D (subunit of RNA polymerase I and II): exon2:c.T332C:p.L111P. Mutations in POLR1D are present in about 5% of individuals diagnosed with TCS. We propose that this mutation is causal in this family, suggesting a pathogenetic link between KFS and TCS.
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http://dx.doi.org/10.1002/ajmg.a.36799DOI Listing
January 2015