Global Advanced Research Journal of Medicine and Medical Sciences (GARJMMS) ISSN: 2315-5159
January 2018, Vol. 7(1), pp. 017-027
Copyright © 2018 Global Advanced Research Journals
Full Length Research Paper
Spotlight into some Abnormalities of Human Chromosome in Saudi Arabia
Saleh A. S. AL-Abdulhadi
Assistant Professor and Consultant, Medical Molecular Genetics, Founder and Chairman of Medical Molecular Genetic Unit, Head of Medical Genetic Division, Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, P.O. Box 422, Riyadh 11942
Accepted 01 December, 2017
Middle Eastern cultures are tribal and heavily consanguineous. Marriage between cousins has been part of the culture for millennia leading to "founder" effect and a large number of genetic diseases. Chromosomal abnormalities are the results of alterations in the number or structure of chromosomes causing significant human morbidity and mortality. They are responsible for a large proportion of miscarriages, developmental delay, and disorders of sexual development, congenital malformations and mental retardation. The aim of this study is to screen some of these frequent observed common chromosomal disorders and try to identify the significant reason behind the increase or present of these diseases in our community. Data collection and survey study into different local hospital in Riyadh and cytogenetic lab with a variety of clinical disorders; Down syndrome (DS), Turner’s syndrome (TS) and Klinefelter syndrome; amenorrhea; ambiguous sex and multiple congenital malformations. The most common autosomal abnormalities were DS. Numerical abnormalities were accounted for 353 (41.0%) and structural abnormalities 18 (2.0%), respectively. Various other chromosomal anomalies were also reported. We have reviewed the incidence and distribution of chromosomal abnormalities and found higher rate of chromosomal abnormalities 43.1% in the referred cases. Our data suggest that chromosomal analysis is important tool in the evaluation of genetic disorders but lack of genetic counseling did not help to understand the high frequency of such rare genetic disorder in our community.
Keywords: Aneuploidy, Autosomes, Cytogenetic analysis, Karyotypes, Sex chromosomes
Abu-Safieh L, Abboud EB, Alkuraya H, Shamseldin H, Al-Enzi S, Al-Abdi L, et al (2011). Mutation of IGFBP7 causes upregulation of BRAF/MEK/ERK pathway and familial retinal arterial macroaneurysms. Am. J. Hum. Genet. 89:313–319.
Abu-Safieh L, Alrashed M, Anazi S, Alkuraya H, Khan AO, Al-Owain M, et al (2013). Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. Genome Res. 23:236–247.
Adly N, Alhashem A, Ammari A, Alkuraya FS (2014). Ciliary Genes TBC1D32/C6orf170 and SCLT1 are mutated in patients with OFD type IX. Hum. Mutat. 35:36–40.
Alangari A, Alsultan A, Adly N, Massaad MJ, Kiani IS, Aljebreen A, et al (2012). LPS-responsive beige-like anchor (LRBA) gene mutation in a family with inflammatory bowel disease and combined immunodeficiency. J. Allergy Clin. Immunol. 130:e482.
Alangari AA, Alsultan A, Osman ME, Anazi S (2013). Alkuraya FS. A novel homozygous mutation in G6PC3 presenting as cyclic neutropenia and severe congenital neutropenia in the same family. J. Clin. Immunol. 33:1403–1406.
Al-Aqeel AI. Al-Aqeel (2005). Sewairi syndrome, a new autosomal recessive disorder with multicentricosteolysis, nodulosis and arthropathy. The first genetic defect of matrix metalloproteinase 2 gene. Saudi Med. J. 26:24–30.
Alazami AM, Adly N, Al Dhalaan H (2011). Alkuraya FS. A nullimorphic ERLIN2 mutation defines a complicated hereditary spastic paraplegia locus (SPG18) Neurogenetics. ;12:333–336
Alazami AM, Al-Owain M, Alzahrani F, Shuaib T, Al-Shamrani H, Al-Falki YH, 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. 33:1429–1434.
Alazami AM, Al-Saif A, Al-Semari A, Bohlega S, Zlitni S, Alzahrani F, et al (2008). Mutations in C2orf37 encoding a nucleolar protein, cause hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome. Am. J. Hum. Genet. 83:684–691.
Alazami AM, Alzahrani F, Bohlega S (2014). Alkuraya FS (2013). SET binding factor 1 (SBF1) mutation causes Charcot-Marie-Tooth disease type 4B3. Neurol. 82:1665–1666.
Alazami AM, Hijazi H, Al-Dosari MS, Shaheen R, Hashem A, Aldahmesh MA, et al. Mutation in ADAT3, encoding adenosine deaminase acting on transfer RNA, causes intellectual disability and strabismus. J. Med. Genet. 50:425–430.
Alazami AM, Hijazi H, Kentab AY (2014). Alkuraya FS. NECAP1 loss of function leads to a severe infantile epileptic encephalopathy. J. Med. Genet. 51:224–228
Albaqumi M, Alhabib FA, Shamseldin HE, Mohammed F (2014). Alkuraya FS. A syndrome of congenital hyperinsulinism and rhabdomyolysis is caused by KCNJ11 mutation. J. Med. Genet. 51:271–274.
Aldahmesh M, Khan A, Hijazi H. Alkuraya F (2013). Homozygous truncation of SIX6 causes complex microphthalmia in humans. Clin. Genet. 84:198–199.
Aldahmesh MA, Abu-Safieh L, Khan AO, Al-Hassnan ZN, Shaheen R, Rajab M, et al (2009). Allelic heterogeneity in inbred populations: the Saudi experience with Alström syndrome as an illustrative example. Am. J. Med. Genet. A. 149:662–665.
Aldahmesh MA, Alshammari MJ, Khan AO, Mohamed JY, Alhabib FA. Alkuraya FS (2013). The syndrome of microcornea, myopic chorioretinal atrophy, and telecanthus (MMCAT) is caused by mutations in ADAMTS18. Hum. Mutat. 34:1195–1199.
Aldahmesh MA, Khan AO, Alkuraya H, Adly N, Anazi S, Al-Saleh AA, et al (2013). Mutations in LRPAP1 are associated with severe myopia in humans. Am. J. Hum. Genet. 93:313–320.
Aldahmesh MA, Khan AO, Mohamed J. Alkuraya FS (2011). Novel recessive BFSP2 and PITX3 mutations: insights into mutational mechanisms from consanguineous populations. Genet. Med. 13:978–981.
Aldahmesh MA, Khan AO, Mohamed JY, Alghamdi MH (2012). Alkuraya FS. Identification of a truncation mutation of acylglycerol kinase (AGK) gene in a novel autosomal recessive cataract locus. Hum. Mutat. 33:960–962.
Aldahmesh MA, Khan AO, Mohamed JY, Hijazi H, Al-Owain M, Alswaid A, et al (2012). Genomic analysis of pediatric cataract in Saudi Arabia reveals novel candidate disease genes. Genet. Med. 14:955–962.
Aldahmesh MA, Li Y, Alhashem A, Anazi S, Alkuraya H, Hashem M, et al (2014). IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome. Hum. Mol. Genet. 23:3307–3315.
Aldahmesh MA, Mohamed JY, Alkuraya HS, Verma IC, Puri RD, Alaiya AA, et al (2011). Recessive mutations in ELOVL4 cause ichthyosis, intellectual disability, and spastic quadriplegia. Am. J. Hum. Genet. 89:745–750.
Aldahmesh MA, Mohammed JY, Al-Hazzaa S. Alkuraya FS (2012). Homozygous null mutation in ODZ3 causes microphthalmia in humans. Genet. Med. 14:900–904.
Al-Dosari MS, Al-Owain M, Tulbah M, Kurdi W, Adly N, Al-Hemidan A, et al (2013). Mutation in MPDZ causes severe congenital hydrocephalus. J. Med. Genet. 50:54–58.
Al-Dosari MS, Shaheen R, Colak D. Alkuraya FS (2010). Novel CENPJ mutation causes seckel syndrome. J. Med. Genet. 47:411–414.
AlHamdan NA, AlMazrou YY, AlSwaidi FM. Choudhry AJ (2007). Premarital screening for thalassemia and sickle cell disease in Saudi Arabia. Genet. Med. 9:372–377.
Al-Jurayyan NA, Al-Nuaim AA, El-Desouki MI, Herbish ASA, Bakr AMA, Swailem AA, et al (1996). Neonatal screening for congenital hypothyroidism in Saudi Arabia: results of screening the first 1 million newborns. Screening. 4:213–220.
Alkuraya F (2013). Impact of new genomic tools on the practice of clinical genetics in consanguineous populations: the Saudi experience. Clin. Genet. 84:203–208.
Alkuraya FS (2010). Autozygome decoded. Genet. Med. 12:765–771.
Alkuraya FS (2010). Homozygosity mapping: one more tool in the clinical geneticist's toolbox. Genet. Med. 12:236–239.
Alkuraya FS. Kilani RA (2001). Attitude of Saudi families affected with hemoglobinopathies towards prenatal screening and abortion and the influence of religious ruling (Fatwa) Prenat. Diagn. 21:448–451.
Alkuraya FS (2013). The application of next-generation sequencing in the autozygosity mapping of human recessive diseases. Hum. Genet. 132:1197–1211.
Almaghlouth I, Mohamed J, Al-Amoudi M, Al-Ahaidib L, Al-Odaib A. Alkuraya F (2012). 5-Oxoprolinase deficiency: report of the first human OPLAH mutation. Clin. Genet. 82:193–196.
Al-Mayouf SM, Sunker A, Abdwani R, Al Abrawi S, Almurshedi F, Alhashmi N, et al (2011). Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat. Genet. 43:1186–1188.
Al-Owain M, Alazami A. Alkuraya F (2011). An autosomal recessive syndrome of severe cognitive impairment, dysmorphicfacies and skeletal abnormalities maps to the long arm of chromosome 17. Clin. Genet. 80:489–492.
Al-Owain M, Al-Zaidan H. Al-Hassnan Z (2012). Map of autosomal recessive genetic disorders in Saudi Arabia: concepts and future directions. Am. J. Med. Genet. A. 158A:2629–2640.
Al-Qahtani A, Khalak HG, Alkuraya FS, Al-hamoudy W, Alswat K, Al Balwi MA, et al (2013). Genome-wide association study of chronic hepatitis B virus infection reveals a novel candidate risk allele on 11q22. 3. J. Med. Genet. 50:725–732.
Alshammari MJ, Al-Otaibi L, Alkuraya FS (2012). Mutation in RAB33B, which encodes a regulator of retrograde Golgi transport, defines a second Dyggve–Melchior–Clausen locus. J. Med. Genet. 49:455–461.
Alsultan A, Shamseldin HE, Osman ME, Aljabri M. Alkuraya FS (2013). MYSM1 is mutated in a family with transient transfusion-dependent anemia, mild thrombocytopenia, and low NK-and B-cell counts. Blood. 122:3844–3845.
Awad S, Al-Dosari MS, AlYacoub N, Colak D, Salih MA, Alkuraya FS, et al (2013). Mutation in PHC1 implicates chromatin remodeling in primary microcephaly pathogenesis. Hum. Mol. Genet. 22:2200–2213.
de Ligt J, Willemsen MH, van Bon BW, Kleefstra T, Yntema HG, Kroes T, et al (2012). Diagnostic exome sequencing in persons with severe intellectual disability. N. Engl. J. Med. 367:1921–1929.
El-Mouzan MI, Al-Salloum AA, Al-Herbish AS, Qurachi MM. Al-Omar AA (2007). Regional variations in the prevalence of consanguinity in Saudi Arabia. Saudi Med. J. 28:1881–1884.
Faqeih E, Shaheen R. Alkuraya FS (2013). WNT1 mutation with recessive osteogenesisimperfecta and profound neurological phenotype. J. Med. Genet. 50:491–492.
Gai X, Ghezzi D, Johnson MA, Biagosch CA, Shamseldin HE, Haack TB, et al (2013). Mutations in FBXL4 encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy. Am. J. Hum. Genet. 93:482–495.
Gupta VA, Ravenscroft G, Shaheen R, Todd EJ, Swanson LC, Shiina M, et al (2013). Identification of KLHL41 mutations implicates BTB-Kelch-Mediated ubiquitination as an alternate pathway to myofibrillar disruption in nemaline myopathy. Am. J. Hum. Genet. 93:1108–1117.
Hijazi H, Salih MA, Hamad MH, Hassan HH, Salih SB, Mohamed KA, et al (2013). Pellagra-like condition is xerodermapigmentosum/Cockayne syndrome complex and niacin confers clinical benefit. Clin. Genet. in press.
Kaiser J (2014). The hunt for missing genes. Science. 344:687–689.
Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR, et al (2014). Global, regional, and national levels and causes of maternal mortality during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet. in press.
Kaya N, Owain MA, AbuDheim N, Zahrani JA, Colak D, Sayed MA, et al (2011). GM2 gangliosidosis in Saudi Arabia: multiple mutations and considerations for future carrier screening. Am. J. Med. Genet. A. 155:1281–1284.
Khalak HG, Wakil SM, Imtiaz F, Ramzan K, Baz B, Almostafa A, et al (2012). Autozygome maps dispensable DNA and reveals potential selective bias against nullizygosity. Genet. Med. 14:515–519.
Lederman MM, Penn-Nicholson A, Cho M, Mosier D (2006). Biology of CCR5 and its role in HIV infection and treatment. JAMA. 296:815–826.
Memish ZA, Saeedi MY (2011). Six-year outcome of the national premarital screening and genetic counseling program for sickle cell disease and β-thalassemia in Saudi Arabia. Ann. Saudi Med. 31:229.
Mohamed JY, Faqeih E, Alsiddiky A, Alshammari MJ, Ibrahim NA. Alkuraya FS (2013). Mutations in MEOX1 encoding mesenchyme homeobox 1, cause klippel-feil anomaly. Am. J. Hum. Genet. 92:157–161.
Moltke I, Grarup N, Jørgensen ME, Bjerregaard P, Treebak JT, Fumagalli M, et al (2014). A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. Nature. in press.
Morales J, Al-Sharif L, Khalil DS, Shinwari J, Bavi P, Al-Mahrouqi RA, et al (2009). Homozygous mutations in ADAMTS10 and ADAMTS17 cause lenticular myopia, ectopialentis, glaucoma, spherophakia, and short stature. Am. J. Hum. Genet. 85:558–568.
Rader DJ. Daugherty A (2008). Translating molecular discoveries into new therapies for atherosclerosis. Nature. 451:904–913.
Rashed M, Ozand P, Harrison M, Watkins P, Evans S. Baillie TA (1994). Electrospray tandem mass spectrometry in the diagnosis of organic acidemias. Rapid Commun. Mass Spectrom. 8:129–133.
Rashed MS, Bucknall MP, Little D, Awad A, Jacob M, Alamoudi M, et al (1997). Screening blood spots for inborn errors of metabolism by electrospray tandem mass spectrometry with a microplate batch process and a computer algorithm for automated flagging of abnormal profiles. Clin. Chem. 43:1129–1141.
Rashed MS, Ozand PT, Bucknall MP. Little D (1995). Diagnosis of inborn errors of metabolism from blood spots by acylcarnitines and amino acids profiling using automated electrospray tandem mass spectrometry. Pediatric Res. 38:324–331.
Rauch A, Wieczorek D, Graf E, Wieland T, Endele S, Schwarzmayr T, et al (2012). Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet. 380:1674–1682.
Reiff RE, Ali BR, Baron B, Timothy WY, Ben-Salem S, Coulter ME, et al (2014). METTL23, a transcriptional partner of GABPA, is essential for human cognition. Hum. Mol. Genet. 23:3456–3466.
Rooryck C, Diaz-Font A, Osborn DP, Chabchoub E, Hernandez-Hernandez V, Shamseldin H, et al (2011). Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome. Nat. Genet. 43:197–203.
Sanjad S, Sakati N, Abu-Osba Y, Kaddoura R. Milner R (1991). A new syndrome of congenital hypoparathyroidism, severe growth failure, and dysmorphic features. Arch. Dis. Child. 66:193–196.
Seidahmed MZ, Salih MA, Abdulbasit OB, Shaheed M, Al Hussein K, Miqdad AM, et al (2012). A novel syndrome of lethal familial hyperekplexia associated with brain malformation. BMC Neurol. 12:125.
Shaheen R, Alazami AM, Alshammari MJ, Faqeih E, Alhashmi N, Mousa N, et al (2012). Study of autosomal recessive osteogenesisimperfecta in Arabia reveals a novel locus defined by TMEM38B mutation. J. Med. Genet. 49:630–635.
Shaheen R, Al-Owain M, Sakati N, Alzayed ZS, Alkuraya FS (2010). FKBP10 and Bruck syndrome: phenotypic heterogeneity or call for reclassification? Am. J. Hum. Genet. 87:306.
Shaheen R, Ansari S, Alshammari MJ, Alkhalidi H, Alrukban H, Eyaid W, et al (2013). A novel syndrome of hypohidrosis and intellectual disability is linked to COG6 deficiency. J. Med. Genet. 50:431–436.
Shaheen R, Faqeih E, Alshammari MJ, Swaid A, Al-Gazali L, Mardawi E, et al (2012). Genomic analysis of Meckel-Gruber syndrome in Arabs reveals marked genetic heterogeneity and novel candidate genes. Eur. J. Hum. Genet. 21:762–768.
Shaheen R, Faqeih E, Seidahmed MZ, Sunker A, Alali FE, Khadijah A, et al (2011). A TCTN2 mutation defines a novel Meckel Gruber syndrome locus. Hum. Mutat. 32:573–578.
Shaheen R, Faqeih E, Shamseldin HE, Noche RR, Sunker A, Alshammari MJ, et al (2012). POC1A truncation mutation causes a ciliopathy in humans characterized by primordial dwarfism. Am. J. Hum. Genet. 91:330–336.
Shaheen R, Faqeih E, Sunker A, Morsy H, Al-Sheddi T, Shamseldin HE, et al (2011). Recessive mutations in DOCK6 encoding the guanidine nucleotide exchange factor DOCK6, lead to abnormal actin cytoskeleton organization and adams-oliver syndrome. Am. J. Hum. Genet. 89:328–333.