Susan T Iannaccone

University of Texas Southwestern Medical Center, Dallas, TX, United States

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Publications (86)391.76 Total impact

  • Diana Castro, Susan T Iannaccone
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    ABSTRACT: Spinal muscular atrophy is caused by mutations in the survival motor neuron 1 (SMN1) gene, leading to the reduction of SMN protein. The loss of alpha motor neurons in the ventral horn of the spinal cord results in progressive paralysis and premature death. There is no current treatment other than symptomatic and supportive care, although over the past decade, there has been an outstanding advancement in understanding the genetics and molecular mechanisms underlying the physiopathology of SMA. The most promising approach, from current trials, is the use of antisense oligonucleotide (ASOs) to redirect SMN2 translation and increase exon 7 inclusion in the majority of the RNA transcript, to increase the production of fully functional SMN protein. Recently, ISIS Pharmaceuticals Inc. (2855 Gazelle Court, Carlsbad CA 92010) reported an interim analysis from a multiple dose study in children with SMA between 2 and 14 years of age, using ASO therapy. The results indicated good tolerability at all dose levels, increases in muscle function in children treated with multiple doses of ISIS-SMNRx, and increase in SMN protein levels in cerebrospinal fluid (CSF) from both single and multiple dose studies. Studies in infants are ongoing in a few centers; soon other institutions may begin enrollment. Infants are fragile and their disease process may differ from the older SMA population. It is not known whether effective drug would best be given to SMA infants or older children. Other promising therapies are still in preclinical phases or early clinical phases. Gene therapy appears to be efficient in improving survival in a severe mouse model of SMA, though a better definition of the route of administration and of the safety profile of the viral vectors is needed before clinical administration is possible.
    Current Treatment Options in Neurology 11/2014; 16(11):316. · 2.18 Impact Factor
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    ABSTRACT: Introduction: Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). Methods: Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. Results: Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. Conclusions: The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges. Muscle Nerve, 2013
    Muscle & Nerve 12/2013; · 2.31 Impact Factor
  • Susan T Iannaccone, Diana Castro
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    ABSTRACT: The purpose of this review is to provide information regarding the diagnosis and natural history of some very rare disorders: congenital muscular dystrophies and congenital myopathies. Patients with these conditions share characteristics such as early onset of weakness and severe hypotonia. Other organs such as the brain, eyes, and skin may be involved. Diagnosis depends largely on recognition of phenotype, muscle biopsy, and mutation analysis. More than 30 genes have been associated with these diseases, most of which have only been recognized in the past decade. Increasing availability of DNA analysis has been important in decreasing delay in diagnosis. Patients with congenital muscular dystrophy or congenital myopathy are at high risk of complications including restrictive lung disease, orthopedic deformities, seizures, cardiomyopathy, and malignant hyperthermia. Life expectancy varies with the severity of complications. Having an accurate and specific diagnosis allows the neurologist to carry out anticipatory guidance and appropriate monitoring. New hope exists for experimental treatments for congenital muscular dystrophy and congenital myopathy as our understanding of pathogenesis evolves.
    Continuum (Minneapolis, Minn.). 12/2013; 19(6 Muscle Disease):1509-34.
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    ABSTRACT: To identify causative genes for centronuclear myopathies (CNM), a heterogeneous group of rare inherited muscle disorders that often present in infancy or early life with weakness and hypotonia, using next-generation sequencing of whole exomes and genomes. Whole-exome or -genome sequencing was performed in a cohort of 29 unrelated patients with clinicopathologic diagnoses of CNM or related myopathy depleted for cases with mutations of MTM1, DNM2, and BIN1. Immunofluorescence analyses on muscle biopsies, splicing assays, and gel electrophoresis of patient muscle proteins were performed to determine the molecular consequences of mutations of interest. Autosomal recessive compound heterozygous truncating mutations of the titin gene, TTN, were identified in 5 individuals. Biochemical analyses demonstrated increased titin degradation and truncated titin proteins in patient muscles, establishing the impact of the mutations. Our study identifies truncating TTN mutations as a cause of congenital myopathy that is reported as CNM. Unlike the classic CNM genes that are all involved in excitation-contraction coupling at the triad, TTN encodes the giant sarcomeric protein titin, which forms a myofibrillar backbone for the components of the contractile machinery. This study expands the phenotypic spectrum associated with TTN mutations and indicates that TTN mutation analysis should be considered in cases of possible CNM without mutations in the classic CNM genes.
    Neurology 08/2013; · 8.30 Impact Factor
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    ABSTRACT: OBJECTIVE:: Juvenile myasthenia gravis (JMG) is an antibody-mediated autoimmune disorder of the neuromuscular junction, at the postsynaptic end plate. JMG presents with fluctuating skeletal muscle weakness and fatigue before the age of 18 years. Very frequently JMG presents with the involvement of the oculomotor muscles, with or without generalized involvement. METHODS:: We performed a retrospective chart review of patients diagnosed with myasthenia in the pediatric neuromuscular clinics at UT Southwestern, between 1990 and 2010. Osserman classification and the response to therapy scale of Millichap and Dodge were used to compare each patient's severity of myasthenia and responsiveness to drugs before the surgery as a baseline and at the last visit, after thymectomy. RESULTS:: Fifty-eight patients were included; 29 (50%) were African American, and 34 (58.6%) were female. Age of onset was 11 months to 17 years, and 38 patients (65%) presented as generalized myasthenia gravis. Forty-nine patients (84%) were acetylcholine receptor antibody (AchR-Ab) positive. Of the 32 to undergo thymectomy, 19 subjects (59%) experienced an improved response to B level on the Myasthenia Scale of Millichap and Dodge (good improvement, both objective and subjective, but continuation of drug therapy required in the same or lower dosage) and 75% experienced a drop in Osserman classification by at least 1. Of the 8 individuals who did not show improvement after thymectomy, 4 subjects (50%) underwent repeat thymectomy. They had initially less invasive fluoroscopic or thoracoscopic procedure. Thymic hyperplasia was found in 7 patients (21%) and thymoma in 2. CONCLUSIONS:: Thymectomy was well tolerated by this group of children. There was clinical improvement after thymectomy in two thirds of the AchR-Ab-positive generalized myasthenia gravis patients. Thymic pathology was seen in less than one third of the patients who underwent thymectomy, with thymic hyperplasia being common. Further studies are necessary to determine whether thymectomy is indicated for all children with generalized JMG. More information about the immunologic, genetic, and molecular differences between patients may determine the best treatment for individual patients.
    Journal of clinical neuromuscular disease 03/2013; 14(3):95-102.
  • Eugenio Mercuri, Enrico Bertini, Susan T Iannaccone
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    ABSTRACT: Spinal muscular atrophy is an autosomal recessive disorder characterised by degeneration of motor neurons in the spinal cord and is caused by mutations of the survival of motor neuron 1 gene SMN1. The severity of spinal muscular atrophy is highly variable and no cure is available at present. Consensus has been reached on several aspects of care, the availability of which can have a substantial effect on prognosis, but controversies remain. The development of standards of care for children with the disorder and the identification of promising treatment strategies have changed the natural history of spinal muscular atrophy, and the prospects are good for further improvements in function, quality of life, and survival. A long-term benefit for patients will be the development of effective interventions (such as antisense oligonucleotides), some of which are in clinical trials. The need to be prepared for clinical trials has been the impetus for a remarkable and unprecedented cooperation between clinicians, scientists, industry, government, and volunteer organisations on an international scale.
    The Lancet Neurology 05/2012; 11(5):443-52. · 21.82 Impact Factor
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    ABSTRACT: Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells, which leads to progressive muscle weakness. Children with SMA type II do not develop the ability to walk without support and have a shortened life expectancy, whereas children with SMA type III develop the ability to walk and have a normal life expectancy. There are no known efficacious drug treatments that influence the disease course of SMA. This is an update of a review first published in 2009. To evaluate whether drug treatment is able to slow or arrest the disease progression of SMA types II and III and to assess if such therapy can be given safely. Drug treatment for SMA type I is the topic of a separate updated Cochrane review. We searched the Cochrane Neuromuscular Disease Group Specialized Register (8 March 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE (January 1991 to February 2011), EMBASE (January 1991 to February 2011) and ISI Web of Knowledge (January 1991 to March 8 2011). We also searched to identify as yet unpublished trials (8 March 2011). We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA types II and III. Participants had to fulfil the clinical criteria and have a deletion or mutation of the survival motor neuron 1 (SMN1) gene (5q11.2-13.2) that was confirmed by genetic analysis.The primary outcome measure was to be change in disability score within one year after the onset of treatment. Secondary outcome measures within one year after the onset of treatment were to be change in muscle strength, ability to stand or walk, change in quality of life, time from the start of treatment until death or full time ventilation and adverse events attributable to treatment during the trial period. Two authors independently reviewed and extracted data from all potentially relevant trials. Pooled relative risks and pooled standardised mean differences were to be calculated to assess treatment efficacy. Risk of bias was systematically analysed. Six randomised placebo-controlled trials on treatment for SMA types II and III were found and included in the review: the four in the original review and two trials added in this update. The treatments were creatine (55 participants), phenylbutyrate (107 participants), gabapentin (84 participants), thyrotropin releasing hormone (9 participants), hydroxyurea (57 participants), and combination therapy with valproate and acetyl-L-carnitine (61 participants). None of these studies were completely free of bias. All studies had adequate blinding, sequence generation and reports of primary outcomes.None of the included trials showed any statistically significant effects on the outcome measures in participants with SMA types II and III. One participant died due to suffocation in the hydroxyurea trial and one participant died in the creatine trial. No participants in any of the other four trials died or reached the state of full time ventilation. Serious side effects were infrequent. There is no proven efficacious drug treatment for SMA types II and III.
    Cochrane database of systematic reviews (Online) 01/2012; 4:CD006282. · 5.94 Impact Factor
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    ABSTRACT: In this study we performed an open-label, pilot study of an orally administered liquid formulation of immediate-release pentoxifylline (PTX) on patients with Duchenne muscular dystrophy (DMD). Treatment efficacy, safety, and tolerability were assessed. The tolerability and safety of PTX and measures of muscle strength and function were evaluated during 12 months of treatment. Seventeen boys with DMD, between 4 and 8 years of age, were enrolled at one of five Cooperative International Neuromuscular Research Group (CINRG) centers. Only 9 were able to complete the 12-month PTX treatment phase; the primary reason for discontinuation was adverse events. Intolerable gastrointestinal side effects were experienced by 65% of participants. Two participants had severe leukopenia that resolved with medication withdrawal. Open-label treatment with a liquid formulation of immediate-release PTX resulted in a high incidence of adverse events in boys with DMD. Poor tolerability of this PTX formulation precluded adequate assessment of efficacy.
    Muscle & Nerve 04/2011; 44(2):170-3. · 2.31 Impact Factor
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    ABSTRACT: Mutations in LMNA cause a variety of diseases affecting striated muscle including autosomal Emery-Dreifuss muscular dystrophy (EDMD), LMNA-associated congenital muscular dystrophy (L-CMD), and limb-girdle muscular dystrophy type 1B (LGMD1B). Here, we describe novel and recurrent LMNA mutations identified in 50 patients from the United States and Canada, which is the first report of the distribution of LMNA mutations from a large cohort outside Europe. This augments the number of LMNA mutations known to cause EDMD by 16.5%, equating to an increase of 5.9% in the total known LMNA mutations. Eight patients presented with either p.R249W/Q or p.E358K mutations and an early onset EDMD phenotype: two mutations recently associated with L-CMD. Importantly, 15 mutations are novel and include eight missense mutations (p.R189P, p.F206L, p.S268P, p.S295P, p.E361K, p.G449D, p.L454P, and p.W467R), three splice site mutations (c.IVS4 + 1G>A, c.IVS6 - 2A>G, and c.IVS8 + 1G>A), one duplication/in frame insertion (p.R190dup), one deletion (p.Q355del), and two silent mutations (p.R119R and p.K270K). Analysis of 4 of our lamin A mutations showed that some caused nuclear deformations and lamin B redistribution in a mutation specific manner. Together, this study significantly augments the number of EDMD patients on the database and describes 15 novel mutations that underlie EDMD, which will contribute to establishing genotype-phenotype correlations.
    Human Mutation 02/2011; 32(2):152-67. · 5.05 Impact Factor
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    ABSTRACT: Spinal muscular atrophy (SMA) is caused by degeneration of anterior horn cells of the spinal cord, which leads to progressive muscle weakness. Children with SMA type I will never be able to sit without support and usually die by the age of two years. There are no known efficacious drug treatments that influence the course of the disease. This is an update of a review first published in 2009. To evaluate whether drug treatment is able to slow or arrest the disease progression of SMA type I, and to assess if such therapy can be given safely. Drug treatment for SMA types II and III is the topic of a separate updated Cochrane review. We searched the Cochrane Neuromuscular Disease Group Specialized Register (8 March 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE (January 1991 to February 2011), EMBASE (January 1991 to February 2011) and ISI Web of Knowledge (January 1991 to 8 March 2011). We searched the Clinical Trials Registry of the U.S. National Institute of Health ( (8 March 2011) to identify additional trials that had not yet been published. We sought all randomised or quasi-randomised trials that examined the efficacy of drug treatment for SMA type I. Participants had to fulfil the clinical criteria and have a deletion or mutation of the SMN1 gene (5q11.2-13.2) confirmed by genetic analysis.The primary outcome measure was time from birth until death or full time ventilation. Secondary outcome measures were development of rolling, sitting or standing within one year after the onset of treatment, and adverse events attributable to treatment during the trial period. Two authors (RW and AV) independently reviewed and extracted data from all potentially relevant trials. For included studies, pooled relative risks and standardised mean differences were to be calculated to assess treatment efficacy. One small randomised controlled study comparing riluzole treatment to placebo for 10 SMA type 1 children was identified and included in the original review. No further trials were identified for the update in 2011. Regarding the primary outcome measure, three of seven children treated with riluzole were still alive at the ages of 30, 48 and 64 months, whereas all three children in the placebo group died; but the difference was not statistically significant. Regarding the secondary outcome measures, none of the children in the riluzole or placebo group developed the ability to roll, sit or stand, and no adverse effects were observed. For several reasons the overall quality of the study was low, mainly because the study was too small to detect an effect and because of baseline differences. Follow-up of the 10 included children was complete. No drug treatment for SMA type I has been proven to have significant efficacy.
    Cochrane database of systematic reviews (Online) 01/2011; · 5.94 Impact Factor
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    ABSTRACT: Congenital muscular dystrophies are a group of rare neuromuscular disorders with a wide spectrum of clinical phenotypes. Recent advances in understanding the molecular pathogenesis of congenital muscular dystrophy have enabled better diagnosis. However, medical care for patients with congenital muscular dystrophy remains very diverse. Advances in many areas of medical technology have not been adopted in clinical practice. The International Standard of Care Committee for Congenital Muscular Dystrophy was established to identify current care issues, review literature for evidence-based practice, and achieve consensus on care recommendations in 7 areas: diagnosis, neurology, pulmonology, orthopedics/rehabilitation, gastroenterology/ nutrition/speech/oral care, cardiology, and palliative care. To achieve consensus on the care recommendations, 2 separate online surveys were conducted to poll opinions from experts in the field and from congenital muscular dystrophy families. The final consensus was achieved in a 3-day workshop conducted in Brussels, Belgium, in November 2009. This consensus statement describes the care recommendations from this committee.
    Journal of child neurology 11/2010; 25(12):1559-81. · 1.59 Impact Factor
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    ABSTRACT: Limb girdle muscular dystrophy (LGMD) is a diverse group of myopathic disorders characterized by proximal muscle weakness and hyperCKemia. Mutations encoding sarcoglycans and numerous other proteins have been shown to be responsible for most cases. We report a series of girls with a negative family history for boys with Duchenne muscular dystrophy, demonstrating an LGMD phenotype associated with dystrophinopathy. A retrospective chart review of all girls presenting with the LGMD phenotype to our clinic between January 2001 and September 2007 was conducted. Patients 18 years old or younger with dystrophinopathy proven by muscle biopsy and/or gene mutations and a negative family history for affected boys were included in the review. Five patients, 4 to 10 years of age at presentation, were included in the series. Four had an LGMD phenotype at presentation. All five patients had hyperCKemia, all five patients had gene mutations, and four patients had muscle biopsy consistent with dystrophinopathy. Dystrophinopathy is an important cause of LGMD phenotype in girls and should be considered in the differential diagnosis.
    Journal of clinical neuromuscular disease 06/2010; 11(4):203-8.
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    ABSTRACT: To evaluate the reliability and validity of the PedsQL 3.0 Neuromuscular Module (NMM) in assessing health-related quality of life in the Duchenne muscular dystrophy (DMD) population for use as a secondary outcome measure in phase III clinical trials. DMD is the most common genetic form of muscular dystrophy in childhood. Clinical trials are underway to evaluate modalities of treatment. The NMM was developed based on interviews of patients with DMD and spinal muscular atrophy. To determine the PedsQL reliability and validity, we administered the NMM to patients with DMD and their caregivers. Boys 8 to 18 years old with DMD were recruited from a neuromuscular disease clinic. At baseline, the child and caregiver completed the NMM and the PedsQL 4.0 Generic Core Scales (GC). The NMM was repeated 2 to 6 weeks later. Reliability was assessed using Cronbach's coefficient alpha (internal consistency) and intraclass correlation (ICC) (test-retest consistency). Construct validity was assessed by comparing baseline child and caregiver NMM total scores with the GC Total Score, forced vital capacity, cardiac ejection fraction, and ambulatory status. Forty-four children and their caregivers completed the study. Internal consistency reliability of the total scale score of the NMM was demonstrated (Child alpha = 0.85; Caregiver alpha = 0.87). Test-retest reliability of the NMM was also demonstrated (Child ICC = 0.75, P = 0.001; Caregiver ICC = 0.85, P < 0.001). Validity of the total scale score of the NMM when compared with the GC Total Scale Score was supported (Child r (41) = 0.63, P < 0.001; Caregiver r (42) = 0.64, P < 0.001). Validity of the NMM compared with forced vital capacity was also supported (Child r (38) = 0.35, P = 0.032; Caregiver r (39) = 0.41, P = 0.01). The NMM parent-proxy-report and child self-report "About My Child's Neuromuscular Disease" scale was significantly related to wheelchair use (P < 0.008 and 0.016, respectively); the GC "Child Self-Report "Physical Health" scale was also significantly related to wheelchair use (P < 0.001). We were unable to conduct any analysis with ejection fraction because of the small number of children across all categories. The PedsQL NMM is a reliable measure of disease-specific health-related quality of life in the DMD population and may be used as an outcome measure in clinical trials.
    Journal of clinical neuromuscular disease 03/2010; 11(3):97-109.
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    ABSTRACT: Clinical research visits are challenging for people with SMA because of limited mobility and intercurrent illnesses. Missing data threaten the validity of research results. Obtaining outcomes remotely would represent a solution. To evaluate reliability of telephone administration of the PedsQL Pediatric Generic Core Quality of Life Inventory 4.0 (Generic) and Neuromuscular Module 3.0 (NM) in SMA, we recruited 21 participants of a Natural History Study for telephone administration of both modules no more than 7 days before or after an in-person study visit. We found excellent reliability between telephone and in-person administration of both modules with the NM slightly better than the Generic. Reliability of the child and parent forms was similar. We concluded that both modules can be administered reliably over the telephone to SMA patients and caregivers, expanding the utility of these tools in clinical trials. Notably, telephone administration is reliable in children as young as 8 years.
    Neuromuscular Disorders 03/2010; 20(3):162-5. · 3.13 Impact Factor
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    ABSTRACT: For Phase II and III clinical trials in children with Spinal Muscular Atrophy (SMA), reliable and valid outcome measures are necessary. Since 2000, the American Spinal Muscular Atrophy Randomized Trials (AmSMART) group has established reliability and validity for measures of strength, lung function, and motor function in the population from age 2 years to 18 years. The PedsQL (Pediatric Quality of Life Inventory) Measurement Model was designed to integrate the relative merits of generic and disease-specific approaches, with disease-specific modules. The PedsQL 3.0 Neuromuscular Module was designed to measure HRQOL dimensions specific to children ages 2-18 years with neuromuscular disorders, including SMA. One hundred seventy-six children with SMA and their parents completed the PedsQL 4.0 Generic Core Scales and PedsQL 3.0 Neuromuscular Module. The PedsQL demonstrated feasibility, reliability, and validity in the SMA population. Consistent with the conceptualization of disease-specific symptoms as causal indicators of generic HRQOL, the majority of intercorrelations among the Neuromuscular Module Scales and the Generic Core Scales were in the medium to large range, supporting construct validity. For the purposes of a clinical trial, the PedsQL Neuromuscular Module and Generic Core Scales provide an integrated measurement model with the advantages of both generic and condition-specific instruments.
    Neuromuscular Disorders 10/2009; 19(12):805-12. · 3.13 Impact Factor
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    ABSTRACT: To evaluate the effect of SMN2 copy number on disease severity in spinal muscular atrophy (SMA), we stratified 45 adult SMA patients based on SMN2 copy number (3 vs. 4 copies). Patients with 3 copies had an earlier age of onset and lower spinal muscular atrophy functional rating scale (SMAFRS) scores and were more likely to be non-ambulatory. There was, however, no difference between the groups in quantitative muscle strength or pulmonary function testing. Functional scale may be a more discriminating outcome measure for SMA clinical trials.
    Muscle & Nerve 10/2009; 40(4):652-6. · 2.31 Impact Factor
  • Neuromuscular Disorders 09/2009; 19(8):606-606. · 3.13 Impact Factor
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    ABSTRACT: Skeletal muscle basal lamina is linked to the sarcolemma through transmembrane receptors, including integrins and dystroglycan. The function of dystroglycan relies critically on posttranslational glycosylation, a common target shared by a genetically heterogeneous group of muscular dystrophies characterized by alpha-dystroglycan hypoglycosylation. Here we show that both dystroglycan and integrin alpha7 contribute to force-production of muscles, but that only disruption of dystroglycan causes detachment of the basal lamina from the sarcolemma and renders muscle prone to contraction-induced injury. These phenotypes of dystroglycan-null muscles are recapitulated by Large(myd) muscles, which have an intact dystrophin-glycoprotein complex and lack only the laminin globular domain-binding motif on alpha-dystroglycan. Compromised sarcolemmal integrity is directly shown in Large(myd) muscles and similarly in normal muscles when arenaviruses compete with matrix proteins for binding alpha-dystroglycan. These data provide direct mechanistic insight into how the dystroglycan-linked basal lamina contributes to the maintenance of sarcolemmal integrity and protects muscles from damage.
    Proceedings of the National Academy of Sciences 08/2009; 106(31):12573-9. · 9.81 Impact Factor
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    ABSTRACT: Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder characterized by extreme paucity of adipose tissue from birth, and early onset of metabolic complications related to insulin resistance. Mutations in three genes, 1-acylglycerol 3-phosphate-O-acyltransferase 2 (AGPAT2), Berardinelli Seip Congenital Lipodystrophy 2 (BSCL2), and Caveolin-1 (CAV1) are associated with the three subtypes of this disorder, CGL1, CGL2 and CGL3, respectively. We report two siblings of Hispanic origin who displayed characteristic features of CGL such as generalized loss of subcutaneous fat from birth, acanthosis nigricans, acromegaloid habitus, umbilical prominence, hepatosplenomegaly, hypoleptinemia, dyslipidemia, and insulin resistance. However, no disease causing variants were detected in the DNA sequence of AGPAT2, BSCL2 or CAV1 genes. Further, whole body magnetic resonance imaging (MRI) in the two siblings revealed marked loss of subcutaneous, intraabdominal and intrathoracic fat like in other patients with CGL, but preservation of bone marrow fat which is invariably lost in all patients with CGL1 and CGL2, but not in the patient reported with CGL3. They also had generalized muscle weakness during infancy and early childhood associated with a nearly fivefold increase in serum creatine kinase (CK) levels, but with normal muscle biopsy and electrophysiologic studies. Both patients were also found to have atlantoaxial dislocation requiring surgical intervention. Thus, this pedigree represents a novel subtype of CGL characterized by generalized loss of body fat but with preservation of bone marrow fat, congenital muscular weakness and cervical spine instability. The genetic basis of this novel subtype remains to be determined.
    American Journal of Medical Genetics Part A 10/2008; 146A(18):2318-26. · 2.30 Impact Factor
  • Petra Kaufmann, Susan T Iannaccone
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    ABSTRACT: Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by muscle atrophy and weakness due to degeneration of the anterior horn cells in the spinal cord. A great need exists for an effective treatment of SMA, a disease that often causes severe disability in patients who are cognitively intact and can have a normal life expectancy. Unlike many other neurologic diseases, SMA can be easily diagnosed through genetic testing. Also, preclinical progress over the last 2 decades has been major, with the discovery of the gene and of a "druggable" modifying gene that provides one of several promising targets for treatment. SMA is rare but is a common orphan disease, so trials should be feasible, raising the hope that we will find effective treatments for this disorder.
    Physical Medicine and Rehabilitation Clinics of North America 09/2008; 19(3):653-60, xii. · 1.09 Impact Factor

Publication Stats

2k Citations
391.76 Total Impact Points


  • 1992–2013
    • University of Texas Southwestern Medical Center
      • • Division of Pediatric Neurology
      • • Department of Pediatrics
      • • Division of Neuro-oncology
      Dallas, TX, United States
  • 2012
    • The Catholic University of America
      Washington, Washington, D.C., United States
  • 1997–2011
    • Texas Scottish Rite Hospital for Children
      Texas City, Texas, United States
  • 2008
    • Columbia University
      New York City, New York, United States
    • The Children's Hospital of Philadelphia
      • Department of Neurology
      Philadelphia, PA, United States
  • 1990
    • University of Cincinnati
      Cincinnati, Ohio, United States
    • Connecticut Children's Medical Center
      Hartford, Connecticut, United States