Fragile X Syndrome (FXS) Helena Bui

Introduction to FXS James Martin, Julia Bell - British physician and geneticist 1943 – X-linked pedigree related to mental disability Martin-Bell Syndrome , Marker X Syndrome Genetic condition  developmental problems, learning disabilities, behavior/mental challenges No racial/ethnic bias Most common in males 1 in 4,000 males vs. 1 in 8,000 females Mutation in FMR1 gene

James Martin and Julia Bell

Cause/Inheritance Cause – FMR1 gene on X chromosome DNA segment (CGG triplet) expanded/repeated 5 to 40 times vs. 200+ (to 1000) times repetition Expansion  silences FMR1  loss of fragile X mental retardation protein production (FMRP) Development of connections between nerve cells 55 to 200 repeats = FRM1 gene premutation, normal but lower amount of FMRP Inheritance – X-linked dominant Mutant gene - on X chromosome Dominant – one copy = enough to cause condition Males XY vs. female XX  males have no extra cover up X  impact more severe Normal, premutation and full mutation Males more affected, only one X

Cause/Inheritance (Pictures) First picture  repeated CCG triplet expansion, differences bewteen normal, premutation and full mutation Second below  location of FMR1 gene on X chromosome Third right  X-linked inheritence

Symptoms Male impact more severe than female Delayed development of speech and language by 2 Tremors, poor coordination, fidgeting, anxiety Mental disabilities  ADD/ADHD, social features of autism, seizures Males: large ears, long face, macroorchidism, connective tissue problems, flat feet, soft skin, Females: 1/3 affected  with significant learning disability Most have moderate symptoms Small percent: no apparent signs at all Behavioral and mental skills affected Macroorchidism – abnormally large testes

Diagnosis Few outward signs in infancy large circumference of head Facial characteristics Signs of mental retardation (especially for females) – cognitive/motor skill delay Prenatal diagnosis with family history of FXS PCR Test (polymerase chain reaction) Short sequence of DNA analysis, amplify sections Looks for expanded mutation (triplet repeat) in FMR1 Blood sample

Treatment No specific treatment, no cure Supportive therapy for affected individuals Special education Decreased stimulation for behavior problems (ADD, ADHD) Vocational/occupational training Highest functioning level as possible Occupational, behavioral

Summary X-Linked dominant disorder Affects males more severely  1 X chromosome FMR1 gene mutation  CGG triplet expansions 200 or more times Silences FMR1 and no FMRP = mental disabilities Behavioral problems Not easily detected outwardly, rely on PCR test No specific cures/treatment but many therapies

Works Cited Board, A.D.A.M. Editorial. Fragile X Syndrome. U.S. National Library of Medicine, 09 June 2011. Web. 28 Nov. 2013. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002633/. "FMR1." - Fragile X Mental Retardation 1. N.p., n.d. Web. 26 Nov. 2013. <http://ghr.nlm.nih.gov/gene/FMR1>. "Fragile X Syndrome." - Genetics Home Reference. N.p., n.d. Web. 27 Nov. 2013. <http://ghr.nlm.nih.gov/condition/fragile- x-syndrome>. "Fragile X Syndrome." National Fragile X Foundation RSS. N.p., n.d. Web. 27 Nov. 2013. http://www.fragilex.org/fragile- x-associated-disorders/fragile-x-syndrome/.

Works Cited (continued) "GeneFacts." GeneFacts. N.p., n.d. Web. 28 Nov. 2013. <http://genefacts.org/index.php?option=com_content>. "Google Images." Google Images. N.p., n.d. Web. 03 Dec. 2013. <http://images.google.com/>. "Learning About Fragile X Syndrome." Learning About Fragile X Syndrome. N.p., n.d. Web. 27 Nov. 2013. <http://www.genome.gov/19518828>. "Who Discovered Fragile X Syndrome?" Who Discovered Fragile X Syndrome? N.p., n.d. Web. 28 Nov. 2013. <http://discovery.yukozimo.com/who-discovered-fragile-x- syndrome/>.