HGM 2011 - Dubai, UAE

Programme

Speakers

Call for Abstracts

Travel Award

Registration

Samia A. Temtamy

Title: Rare Autosomal Recessive Disorders in Egyptians

The Egyptian contribution to medicine and genetics is justly reasoned. Ancient Egypt gives us some of the earliest evidence for both congenital and acquired diseases. Although birth incidence studies of congenital malformations have shown that the overall incidence of malformations as a whole is similar to other populations, there is a relative excess of autosomal recessive disorders due to the high rate of consanguinity. Among 200 genetic disorders reported in Egyptians 70% were autosomal recessive. The presentation provides a review of reported rare autosomal recessive genetic disorders among Egyptians with emphasis on their clinical features and molecular bases. Data are collected from available studies mostly from personal experience of the speaker over the last forty years. Some disorders have been identified for the first time in the world by the speaker. Examples of the novel syndromes are Carpenter syndrome (MIM 201000), Temtamy syndrome of multiple congenital anomaly, mental retardation, agenesis of the corpus callosum ,eye colobomas,subluxatio of lenses, facial dysmorphism and connective tissue dysplasia(MIM 218340),the syndrome of congenital cataract,hirsutism and mental retardation (CAHMR syndrome MIM 211770) and Temtamy preaxial brachydactyly syndrome (MIM 605282). Autosomal recessive inheritance was suggested or confirmed for some disorders; examples are the Marden-Walker syndrome (248700) and a variant of Adams-Oliver syndrome (218600) ,and autosomal recessive variants of osteogenesis imperfecta. Molecular studies of rare autosomal recessive disorders in Egyptians also helped in the identification of new gene mutations. Examples are Fanconi anemia (MIM 227650), Ellis-van Creveld syndrome (MIM 225500) the 3M syndrome (MIM 273750), and the Ostrix gene mutation in osteogenesis imperfecta.

The recently identified molecular basis of Temtamy preaxial brachydactyly syndrome and of Cenani-Lenz syndrome (MIM 212780) will be outlined.

In conclusion, molecular studies defined locus heterogeneity of rare autosomal recessive disorders and increased our knowledge of molecular pathways. Because of the rarity of these disorders, international networking is needed to discover the genes responsible for other rare autosomal recessive disorders which have not yet been identified. Considering ethical regulations, data base registeries, backed up with DNA banks should be encouraged. Transfer of recent molecular technologies, at a reasonable cost, is needed from the advanced to the developing world scientists. Large scale functional genomic studies will permit genotype/phenotype correlations. The results will also allow better genetic counseling, carrier detection, prenatal and preimplantation diagnosis necessary for the prevention of such chronic and crippling disorders.

Selected references:

Temtamy, S.A.: Carpenter's Syndrome: Acrocephalopolysyndactly, An autosomal recessive syndrome; J. Pediatrics1966s. 69: 111-120

Temtamy, S.A.: and Sinbawy, A.H.: “Cataract, hirsuitism and mental retardation (CAHMR). A new autosomal recessive syndrome. Amer., J. Med. Genet., 1991. 41: 432-434

Temtamy SA,: et al. New autosomal recessive multiple congenital abnormalities/mental retardation syndrome with craniofacial dysmorphism absent corpus callosum, iris colobomas and connective tissue dysplasia. Clinical Dysomorphology. 1996. 5, 23-240,

Hanson DE, Black GCM, Murray PG.Sud A, Temtamy SA, Aglan M,S et al..The primordial growth disorder 3-M syndrome connects ubiquitation to the cytoskeletal adaptor OBSL1.American Journal of Human Genetics 2009.84,801-806 .

Yun Li,..,Temtamy SA etal. LRP4 Mutations Alter Wnt/b-Catenin Signaling and Cause Limb and Kidney Malformations in Cenani-Lenz Syndrome. The American Journal of Human Genetics 2010, 86:696-70.

LapunzinaI, AglanM, TemtamySA, et al . Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta,American Journal of Human Genetics,2010,87:110-114.

LiY, LaueK, Temtamy S, etal. Temtamy preaxial brachydactyly syndromeis caused by loss-of-function mutations in Chondroitin synthase 1, a potential target of BMP signaling. Am J.Hum Genet Hum Genet, 87: 757-767, 2010

Sheikh Hamdan Bin Rashid Al Maktoum
Award for Medical Science

Human Genome Organisation

Centre for Arab Genomic Studies