Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease. This simplistic assumption would sometimes be incorrect. The most common cause of genetic disorders is multifactorial inheritance which includes genes and environmental factors. Single gene disorders appear in about 1/100 newborn and chromosomall abnormalities in about 1/150. Gene symbols are written in BOLD ITALICS. The indicated gene may be mutated, deleted, duplicated, or translocated to a different location. Nearly two thousand genes are mentioned. Ongoing research provides new information so that specific details need frequent updating. The reader is reminded that this is of necessity a work in progress: we will update information as it becomes available. Comments and suggestions from readers are welcomed. A. Name Gene Comments Aarskog-Scott, FGDY, FGD1, AAS Females are only partly affected, males have lax joints, abnormal facial-digital-genital at Xp11.21,or at Xq13. cervical vertebrae, short stature, shawl scrotum, clinodactyly, and syndrome. hypertelorism. (XR, XD). MIM 100050 Aase-Smith syndrome-I. PHA3 at 17p11-q21 Hydrocephalus, Dandy-Walker malformation, congenital joint (AD). MIM 147800 contractures, congenital neuroblastoma, ventricular septal defects, cleft palate, ptosis, and death in infancy. See distal arthrogryposis-IIB (MIM 601680), Marden-Walker (MIM 108120, 248700), and Gordon syndromes (MIM 114300). Aase-Smith syndrome-II. Gene Congenital hypoplastic anemia, triphalangeal thumbs, and distal (AD). MIM 205600 arthrogryposis. Compare with Diamond-Blackfan anemia.(AR, AD), DBA at 19q13.2. (MIM 205900 abetalipoproteinemia APOB at 2p24-p22 Bassen-Kornzweig syndrome, unable to synthesize the (AR). MIM 200100, 107730 for a microsomal apolipoprotein B peptide of low density lipoprotein, fail to absorb triglyceride-transfer and transport lipoproteins, have hypolipoproteinemia, protein. hypocholesterolemia, coronary artery disease, ataxia, muscle weakness, kyphosis, slurred speech. Signs develop after age 10. May have ptosis, nystagmus, ophthalmoplegia, macular degeneration, and retinopathy. Treat with vitamins A and E. See also Abelson leukemia (AD) ABL at 9q34.1 (MIM 189980) abetalipoproteinemia. (AR) MTP at 4q22-q24 A defect in a microsomal triglyceride transfer protein causes another abetalipoproteinemia. ABO blood type (AD) ABO at 9q34 More risk of peptic ulcer and thromboembolic disease. See adenylate kinase deficiency. (MIM 103000). acanthocytosis . AEI, EPB3, SLC4A1 Have spherocytosis and anemia. (S, AR, AD) at 17q21-q22. See MIM 100500, 200150. acanthosis nigricans (AD) INSR at 19p13.3. Insulin receptor gene. See diabetes. acatalasemia. (AD) CAT at 11p13. Takahara disease with ulcers of the gums. Achard syndrome. Gene A connective tissue disorder, an atypical Marfan syndrome, (AD). MIM 100700 arachnodactyly, with micrognathia and ligament and joint laxity in hands and feet. May be similar to Marfan syndome. (MIM 154700). See also Achard-Levi syndrome which can be caused by a midbrain stroke. Have dysostosis and ligament laxity. See also Achard-Thiers syndrome, diabetes in bearded women. achondrodysgenesis DTD, DTDST Diastrophic dysplasia. Subtypes include: type 1 ACG1A (MIM (AR, rarely AD) at 5q32-q33 200600), type 2 ACG2 (MIM 200610), type 3 (MIM 200710), and MIM 222600 . type 4 (MIM 200720). See MIM 200700 for Grebe (AR) dysplasia CDMP1 at 20q11.2 (MIM 601146), CDMP2, (MIM 601147). achondroplasia ACH, FGFR3 at 4p16.3 Robinow-Silverman-Smith syndrome, incidence 1/20,000, with (S, AD, AR). MIM 134934 is a negative regulator dwarfism, skeletal anomalies, deafness, strabismus, hyperopia, of bone growth. and optic atrophy. Achondroplasia is the commonest skeletal dysplasia and produces the most frequent form of short-limb dwarfism. achondrodysgenesis- COL2A1 Short-limb dwarfism. hypochondro-dysgenesis-II. at 12q13.11-q13.2 (AD) F syndrome Gene may be Acropectorovertebral syndrome, skeletal dysplasia, and often (AD). MIM 102510 LMBR1 at 7q36 syndactyly. ACHOO syndrome Gene May affect 25% of the population. (AD). MIM 100820 A photic stimulus induces a single or a multiple sneeze reflex. achromatopsia. (AR) See color vision. Ackerman glaucoma. (AR) Gene Have juvenile glaucoma and dental defects. acrocephalopoly-syndactyly. FGFR2 at 10q25.3-q26 See Pfeiffer, formerly Noack syndrome, also called ACSV. ACPS. type I. (AR, AD) Craniosynostosis, broad thumb and great toe, and polysyndactyly. ACPS. type II. FGFR2 at 10q25.3-q26 Carpenter syndrome with mental retardation, craniosynostosis, (AR). MIM 201000 preaxial polydactyly, brachydactyly, syndactyly, and corneal opacities. Is a severe form of Apert syndrome. (MIM 101200). ACPS. type III Genes. Sakati-Nyhan-Tisdale syndrome is rare. (AD). MIM 101120 Craniosynostosis, acrocephaly, leg hypoplasia, preaxial polydactyly, and hypertelorism. ACPS. type IV Genes. The Goodman and Summitt syndromes are both variants of zaeus . MIM 201020, 272350 Carpenter syndrome, with obesity, acrocephaly, syndactyly, and polydactyly. acrocephalosyndactyly, FGFR2 at 10q25.3-q26 Apert syndrome is also called ACPS2, incidence 1/130,000, signs ACS. type I. are. oxycephaly (tower skull), parrot-beaked nose, (AD, AR). MIM 101200 hydronephrosis, syndactyly, hypertelorism, exophthalmos, and external strabismus. Mutations in FGFR2 are involved in several syndromes: Apert (MIM 101200), Carpenter (MIM 201000), Crouzon (MIM 123500), Jackson-Weiss (MIM 123150), and others. ACS. type II TWIST at 7p22-p21 Robinow-Sorauf syndrome patients may have polydactyly of the (AD). MIM 180750 great toes but otherwise resemble Saethre-Chotzen syndrome. ACS. type III SCS, TWIST Saethre-Chotzen syndrome, signs are craniosynostosis, pointed (AD). MIM 101400 at 7p22-p21 nose, cleft palate, heart defect, hypertelorism, and strabismus. A few have learning disability or are mentally retarded. ACS. type IV ACS IV Also called Robinow -Sorauf syndrome. Clinodactyly, (AD). MIM 180750 camptodactyly, ulnar deviation, hypertelorism, and strabismus. Resembles Saethre-Chotzen syndrome (AD) (MIM 101400). ACS. type V FGFR2 at 10q25.3-q26, See Pfeiffer, Crouzon, Noack, and Apert syndromes. (AD) MIM 101600 FGFR1 at 8p11.2-p11.1 Can also cause cancer. acoustic neuroma. (AD, S) NF2 at 22q12.2 Compare with NF1 at 17q11.2. acrodermatitis enteropathica Gene may be Zinc deficiency manifests in infancy, acrodermatitis, diarrhea, and (AR). MIM 201100 SLC39A4 at 8q24. failure to thrive. acrofacial dysostosis (AD) AFDN at 9q32 See Nager syndrome. (MIM 154400) acromegaloid changes, ACL Rosenthal-Kloepfer syndrome onset by age 1 year. cutis verticis gyrata, Tall with large hands and feet, longitudinal folds in scalp skin, and corneal leukoma pituitary tumors, keratitis and bilateral corneal leukomas. (AD). MIM 102100 acrorenoocular or Gene Thumb hypoplasia, polydactyly, horseshoe kidney, mental acral-renal-ocular syndrome retardation, Duane anomaly (MIM 126800), ptosis, and optic (AD, AR). MIM 102490 nerve colobomas. (MIM 126800). acromicric dysplasia. Gene Severe growth retardation, short hands and feet, carpal tunnel (AD). MIM 102370 syndrome, hoarse voice, and mild facial anomalies. See Moore-Federman syndrome (AD), (MIM 127200). acute retinal necrosis ARN or BARN Bilateral retinal necrosis is mostly caused by a herpes infection. syndrome See Leigh syndrome. (MIM 256000), and can occur with a varicella-zoster virus infection. acyl CoA dehydrogenase ACADS, SCAD Short chain type, very rare.. Deficiency of mitochondrial short deficiency. type 1. on chromosome 12 chain acyl, CoA, butyryl CoA.. Can manifest in infancy or later (AR). MIM 201470 in life. acyl CoA dehydrogenase ACADH, ACADM at 1p31. Medium chain type, carnitine deficiency, CACT at 3p21.31. deficiency. type 2. A deficiency of acyl CoA occurs in 1/10,000 births. (AR). MIM 201450 With this deficiency the child can die at about age 2 years. Some have Reye syndrome, (AR) SCD at 5q31.1(MIM 212140) adrenal unresponsiveness.. acyl CoA dehydrogenase ACADL, LCAD Long chain type. LCAD deficiency has its onset before age 6 deficiency.