My research efforts encompass both clinical and basic projects focused on molecular genetics, diagnostics and therapeutics for neuromuscular diseases in children.
My basic science work has led to the publication of several important papers in the investigation of DMD (Duchenne muscular dystrophy). Colleagues and I described for the first time in a 1987 Nature publication the phenomenon of germ-line mosaicism in DMD, in which a female with negative blood-based DNA testing for carrier status may still be a carrier and thus be at risk for transmitting the disease to her children. Identifying this biological phenomenon in DMD has had important implications for the genetic counseling of DMD families.
I am committed to basic research and collaborate with scientists in the Enders and CLS research laboratories of Boston Children's Hospital as well as other institutions on the description of novel mutations in patients with neuromuscular diseases and the application of new technologies to explore the pathogenesis of congenital myopathies and muscular dystrophies.
My clinical research focuses on DMD and SMA (spinal muscular atrophy). I have led several pivotal clinical trials to test mutation specific treatments for these diseases. A series of clinical trials of an antisense oligonucleotide given via spinal tap for SMA has shown encouraging results. I lead one of a few centers in the United States currently testing this treatment and other treatments for SMA and DMD.
My clinical studies have also investigated arthrogryposis multiplex congenita (AMC), chronic inflammatory demyelinating neuropathy (CIDP), and the development of diagnostic algorithms for evaluating children with metabolic myopathies and other neuromuscular diseases.
Remarkable progress in the field of neuromuscular diseases has introduced new genetic tests and has changed the indications for utilization of certain diagnostic procedures in the evaluation of children with presumed disorders of the motor unit. In articles and chapters published in the last few years, I have attempted to define the indications for the new diagnostic tests and re-delineate the role of traditional procedures such as electromyography and muscle biopsy.
I am proud to have written the only major, comprehensive textbook on pediatric neuromuscular disorders, Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach, the most comprehensive text in pediatric neuromuscular diseases ever published, with more than a thousand copies sold world-wide in the first few months after the release of the second edition in 2015. I am the author of over 140 peer-reviewed publications and over 80 book chapters, including:
Kunkel LM, Hejtmancik JF, Caskey CT, Speer A, Monaco AP, Middlesworth W, Colletti CA, Bertelson C, Müller U, Bresnan M, Shapiro F, Tantravahi U, Speer J, Latt SA, Bartlett R, Pericak-Vance MA, Roses AD, Thompson MW, Ray PN, Worton RG, Fischbeck KH, Gallano P, Coulon M, Duros C, Boue J, Junien C, Chelly J, Hamard G, Jeanpierre M, Lambert M, Kaplan JC, Emery A, Dorkins H, McGlade S, Davies KE, Boehm C, Arveiler B, Lemaire C, Morgan GJ, Denton MJ, Amos J, Bobrow M, Benham F, Boswinkel E, Cole C, Dubowitz V, Hart K, Hodgson S, Johnson L, Walker A, Roncuzzi L, Ferlini A, Nobile C, Romeo G, Wilcox DE, Affara NA, Ferguson-Smith MA, Lindolf M, Kaariainen H, de la Chapelle A, Ionasescu V, Searby C, Ionasescu R, Bakker E, van Ommen GJ, Pearson PL, Greenberg CR, Hamerton JL, Wrogemann K, Doherty RA, Polakowska R, Hyser C, Quirk S, Thomas N, Harper JF, Darras BT, Francke U. Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy. Nature 1986;322:73-77.
Darras BT, Harper JF, Francke U. Prenatal diagnosis and detection of carriers in Duchenne's muscular dystrophy. N Engl J Med 1987;316:985-992.
Darras BT, Francke U. A partial deletion of the muscular dystrophy gene transmitted twice by an unaffected male. Nature 1987;329:556-558.
Darras BT, Koenig M, Kunkel LM, Francke U. Direct method for prenatal diagnosis and carrier detection in Duchenne’s/Becker’s muscular dystrophy using the entire Dystrophin cDNA. Am J Med Genet 1988;29:713-726.
Darras BT. Molecular genetics of Duchenne and Becker muscular dystrophy. J Pediatr 1990;117:1-15.
Darras BT, Jones HR. Diagnosis of pediatric neuromuscular disorders in the era of DNA analysis. Pediatr Neurol 2000;23(4):289-300.
Wu JY, Kuban K, Allred EN, Darras BT. Association of Duchenne muscular dystrophy with autism spectrum disorder. J Child Neurol 2005;20:790-795.
Markowitz JA, Singh P, Darras BT. Spinal muscular atrophy: a clinical and research update. Pediatr Neurol 2012;46(1):1-12.
Singh P, Liew WK, Darras BT. Current advances in drug development in spinal muscular atrophy. Curr Opin Pediatr 2013 Dec;25(6):682-8.
Darras BT, Markowitz JA, Monani UR, De Vivo DC. Spinal muscular atrophies. In: Darras BT, Jones HR Jr, Ryan MM, De Vivo DC, editors. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach. Second edition. San Diego: Academic Press, 2015.
Darras BT, Menache-Starobinski CC, Hinton V, Kunkel LM. Dystrophinopathies. In: Darras BT, Jones HR Jr, Ryan MM, De Vivo DC, editors. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach. Second edition. San Diego: Academic Press, 2015.
Darras BT, Jones HR Jr, Ryan MM, De Vivo DC, editors. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach. Second edition. San Diego: Academic Press, 2015.