Gene: [06p213/RDD] dyslexia, developmental (reading disability); [DLX1 ]

COM

 [1] In the OMIM, this locus with its gene symbol DLX1 was assigned to Chr 15q11, based on data published by Smith-1983. Those authors analyzed linkage of autosomal dominant specific dyslexia in nine three-generation families and revealed a significant lod score (Z=3.241 at the teta = 0) with Chr 15 heteromorphic variants detected by sequential Q-to-C banding. However, all of the further studies (Fain-1985; Bisgaard-1987; Rabin-1993) did not confirm the linkage of the disease phenotype on Chr 15 (also see a Smith-Kimberling's reinverstigation of earlier studied kindreds, in: Reading Disabilities: Genetic and Neurological Influences, Pen- nigton B, Ed, Kluwer Academic, Boston, 1991). In addition, independently obtained data on possible linkage of dyslexia both with the Rh region on Chr 1 (Rabin-1993) and with a translocation between Chr 1p and 2q (Froster-1993) also are yet not confirmed.
[2] The symbol DLX1 has already been assigned to the distal-less homeotic gene (GEM:02q32/DLX1); hence, the usage of DLX for a designation of any dyslexia locus is not appropriate."

PHE

 [1] An old, rarely used term for the disease is 'congenital word blindness' introduced by W.P.Morgan in 1896 (Brit Med J, vol.2, 1378).
[2] Unlike 'alexia' that denotes the inability to understand the meaning of written symbols, in general, 'dyslexia' is currently applied to conditions in which (according to the USA Diagnostic and Statistical Manual of Mental Disorders, DSM-III-R) there is 'marked impairment in the development of word recognition skills and reading comprehension that is not explainable by mental retardation or inadequate schooling and that is not due to a vision or hearing defect or a neurologic disorder'. In addition, according to a definition adopted by the World Federation of Neurology, specific dyslexia 'is dependent upon fundamental cognitive disabilities which are frequently of constitutional origin'. Thus, the condition in question is a congenital and, particularly developmental disorder which is characterized by noticeable difficulties in acquiring skills to read words (and not infrequently to spell and write them as well) although affected persons are sensorily normal and often demonstrate well-developed intellectual abilities.
[3] Criteria of practical diagnostics of the disorder widely vary in different clinical schools. In many cases, it is not an ordinary diagnostic task to distinguish dyslexia as a possible (but non-obligatory) symptom among the other learning difficulties, for example, in Attention-deficit/hyperactivity disorder (ADHD) from dyslexia as specific developmental disorders. In turn, this fact essentially affects final estimations and data obtained in neuro-anatomical, epidemiological, and genetic studies of the specific dyslexia.
[4]-For detailed information on clinical aspects of the disorder, see the following textbooks:
(1) Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, DSM-IV. American Psychiatric Association, Washington, DC, 1994; pp. 46-53.
(2) Diseases of the Nervous System: Clinical Neurobiology. Eds: A.K.Asbury et al., W.B.Saunders C., Philadelphia, 1992; vol. 1: 636-645.
(3) Comprehensive Textbook of Psychiatry/V. Eds: H.I.Kaplan, B.J. Sadock, Williams & Wilkins, Baltimor, 1989; vol. 1: 146-147, 226; and vol. 2: 1788-1796."

FOG

 [1] Estimates of the prevalence rate for dyslexia widely vary in different studies since there are different interpretations of the disease phenotype. In the past, the commonly accepted estimates varied from 5 to 10% of the school-age population when broader criteria of a Developmental Learning Disorder diagnosis were applied; and those varied around 4% when narrower criteria of the specific dyslexia diagnosis were used. Likewise, in many earlier studies of dyslexia, all authors noted that affected boys among their patients occurred significantly more often than affected girls (in accordance with the ratio of 4 to 1). One of the other possible causes of the phenomenon have been recognized due to several studies (Shaywitz-1990) which noticed that boys more frequently display disruptive behaviors in association with Learning Disorders. Within familial samples, the male-to-female ratio has been found to be lower (approximately 2 to 1) when stricter diagnostic criteria are used rather than common school-based referral procedures. The mentioned facts should carefully be considered before any of the epidemiological estimations will be used by applying modern sophisticated methods of genetic linkage analysis of the disease in question.
[2] Two important facts support genetic causes of reading disability - (i) a higher prevalence rate of dyslexia among the first-degree relatives of dyslexic probands (approximately 35-45% for males and almost 20% for females) in comparing with that for the population at large (approximately 4-6%); and (ii) a higher concordance rate for dyslexia among MZ twin pairs (87% at an average) than DZ twin pairs (29%). However, likewise regarding many multifactorial diseases, different conclusions on a mode of dyslexia inheritance have been published in the recent past. For example, Zahalkova-1972 suggested that the main disease phenotype is inherited as an autosomal dominant with reduced penetrance in females whereas Finucci-1976 did not find bases to support any specific mode of inheritance, except a general idea on genetic heterogeneity of dyslexia. During the past 10 years, results obtained in several independent studies pointed to a possible involvement of the HLA antigenes in pathogenesis of dyslexia, at least some of its family forms. Based on this data, a purposeful linkage analysis of the disease with the HLA region on Chr 6p has recently been performed."

LOC

 In a recent report (Cardon-1994), the authors have presented a detailed description of new data strongly supporting linkage of dyslexia with some markers mapped on Chr 6p inside the HLA region. Among several studied markers (GLO1, BF, TNFB, anonymous RFLPs - pTHH157, 2C5, and PCR mediated single copies of D6S87, -S89, -S105, -S109 as well), TNFB and D6S105 revealed very tight linkage with the disease phenotype. These two markers are located within a 2 cM distance on the chromosome subsegment 6p21.3."

REF

 LOC,LIN,CYG "Bisgaard ML &: Clin Genet, 32, 118-119, 1987
LOC,LIN,CYG "Cardon LR &: Science, 266, (Oct 14), 276-279, 1994
FOG,POP "DeFries JC &: J Learn Disabil, 22, 544-545, 1989
FOG,POP "DeFries JC &: Nature, 329, 537-539, 1987
FOG,POP "DeFries JC &: Brit J Psychiat, 132, 361-367, 1978
LOC,LIN,CYG "Fain PR &: CCG, 40, (HGM8), 625, 1985
PHE,PAT "Felton RH, Wood FB: J Learn Disabil, 22, 3-22, 1989
FOG,POP "Finucci JM &: Ann Hum Genet, 40, 1-23, 1976
LOC,LIN,CYG "Froster U &: Lancet, 342, N8864, 178-179, 1993
PHE,PAT "Galaburda AM: Ann Dyslexia, 39, 67-80, 1989
FOG,POP "Galaburda AM, Kemper: Trans Am Neurol Assoc, 103, 262-265, 1978
FOG,HIS,REV "Hallgren B: Acta Psych Neurol Scand, 65, (Suppl), 1-287, 1950
FOG,HIS,REV "Herschel M: Hum Genet, 40, 115-134, 1978
FOG,HIS,REV "Lewitter FI &: Behav Genet, 10, 9-30, 1980
FOG,POP "Omenn GS, Weber B: Am J Med Genet, 1, 333-342, 1978
FOG,POP "Pennington BF &: JAMA, 266, N11, 1527-1534, 1991
LOC,LIN,CYG "Rabin M &: Lancet, 342, 178, 1993
PHE,PAT "Rosenberger PB: New Engl J Med, 326, 192-193, 1992
PHE,PAT "Shaywitz SE &: New Engl J Med, 326, 145-150, 1992
FOG,POP "Shaywitz SE &: JAMA, 264, 998-1002, 1990
FOG,POP "Smith SD &: J Am Acad Child Adolesc Psychiat, 29, 204-213, 1990
LOC,LIN,CYG "Smith SD &: Science, 219, 1345-1347, 1983
FOG,POP "Zahalkova M &: J Med Genet, 9, 48-52, 1972

KEY

 neu

CLA

 unknown, basic

LOC

 06 p21.3

MIM

 MIM: 127700

SYN

 DLX1