Abstract
Whole-exome sequencing (WES) is an ideal method for the diagnosis of autosomal recessive diseases. The aim of this study was to evaluate the diagnostic power of WES in patients with autosomal recessive inheritance and to determine the relationship between genotype and phenotype. Retrospective screenings of 24 patients analysed with WES were performed and clinical and genetic data were evaluated. Any pathogenic mutation that could explain the suspected disease in 4 patients was not identified. A homozygous pathogenic mutation was detected in 18 patients. 2 patients had heterozygous mutations. According to this study results, WES is a successful technique to be used at the stage of diagnosis in patients who are accompanied by various degrees of intellectual disability matching the inheritance of the autosomal recessive.
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References
ACMG Policy Statement (2012) Points to consider in the clinical application of genomic sequencing. Genet Med 14(8):759–761
Alazami AM et al (2012) Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism. Hum Mutat 33(10):1429–1434
Angius A et al (2018) Erratum: Bi-allelic mutations in KLHL7 cause a crisponi/CISS1-like phenotype associated with early-onset retinitis pigmentosa. [Am J Hum Genet (2016) 99(1):(236–245) (S0002929716301616) (https://doi.org/10.1016/j.ajhg.2016.05.026)]. Am J Hum Genet 102(4):713
Azmanov DN et al (2013) Challenges of diagnostic exome sequencing in an inbred founder population. Mol Genet Genom Med 1(2):71–76
Finster M, Wood M (2005) The Apgar score has survived the test of time. Anesthesiology 102(4):855–857
Gilissen C, Hoischen A, Brunner HG, Veltman JA (2012) Disease gene identification strategies for exome sequencing. Eur J Hum Genet 20(5):490–497. https://doi.org/10.1038/ejhg.2011.258
Tassé MJ, Grover MD (2013) American association on intellectual and developmental disabilities. In: Volkmar FR (ed) Encyclopedia of autism spectrum disorders. Springer, New York, pp 122–125
Harripaul R et al (2017) Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families. Mol Psychiatry 23(4):973
Harripaul R, Noor A, Ayub M, Vincent JB (2017) The use of next-generation sequencing for research and diagnostics for intellectual disability. Cold Spring Harb Perspect Med 7(3):a026864
Khan E, Khan J, Rafi M, Khan F (2017) Consanguinity and autosomal recessive mental retardation in South Waziristan Agency. J Health Sci 7(3):44–49
MacLennan AH, Thompson SC, Gecz J (2015) Cerebral palsy: causes, pathways, and the role of genetic variants. Am J Obstet Gynecol 213(6):779–788
Mccandless SE, Brunger JW, Cassidy SB (2004) The burden of genetic disease on inpatient care in a children’s hospital. Am J Hum Genet 74:121–127
Nelson KB, Dambrosia JM, Ting TY, Grether JK (1996) Uncertain value of electronic fetal monitoring in predicting cerebral palsy. N Engl J Med 334(10):613–619
Oechsli FW et al (1989) Prenatal and perinatal factors in the etiology of cerebral palsy. J Pediatr 116(4):615–619
Pharoah POD (2007) Prevalence and pathogenesis of congenital anomalies in cerebral palsy. Arch Dis Child Fetal Neonatal Ed 92(6):F489–F493
Picciolini O et al (2006) Usefulness of an early neurofunctional assessment in predicting neurodevelopmental outcome in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed 91(2):111–118
Reddihough D, Collins K (2003) Epidemiology and causes of cerebral palsy. Aust J Physiother 49:7–12
Rymen D et al (2012) COG5-CDG: expanding the clinical spectrum. Orphanet J Rare Dis 7(1):1–10
Rymen D et al (2015) Key features and clinical variability of COG6-CDG. Mol Genet Metab 116(3):163–170. https://doi.org/10.1016/j.ymgme.2015.07.003
Samaranch L et al (2008) SPG11 compound mutations in spastic paraparesis with thin corpus callosum. Neurology 71(5):332–336
Shashi V et al (2014) The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders. Genet Med 16(2):176–182
Thorngren-Jerneck K, Herbst A (2001) Low 5-minute Apgar score: a population-based register study of 1 million term births. Obstet Gynecol 98(1):65–70
TÜİK. 207AD (2017) Türkiye İstatistik Kurumu, İstatistiklerle Yaşlılar. TÜİK. http://www.tuik.gov.tr/PreHaberBultenleri.do?id=27595
Verma A, Srivastava P, Kumar P (2016) Stress among parents having children with mental retardation: a gender perspective. J Disabil Manag Rehabil 2(1979):68–72
Vissers LELM, Gilissen C, Veltman JA (2015) Genetic studies in intellectual disability and related disorders. Nat Rev Genet 17(1):9–18. https://doi.org/10.1038/nrg3999
Witters I, Moerman P, Fryns J-P (2002) Fetal akinesia deformation sequence: a study of 30 consecutive in utero diagnoses. Am J Med Genet 113(1):23–28
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Elmas, M., Yıldız, H., Erdoğan, M. et al. Comparison of clinical parameters with whole exome sequencing analysis results of autosomal recessive patients; a center experience. Mol Biol Rep 46, 287–299 (2019). https://doi.org/10.1007/s11033-018-4470-7
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DOI: https://doi.org/10.1007/s11033-018-4470-7