Jamshed Khan, Muhammad Junaid, Shahab Uddin, Khalida Moeed, Usman Ullah, Shehla Aman


Background: Intellectual disability (ID) is a neuro-developmental defect that is manifested by development delay and learning disability. Such defects may be caused due to chromosomal disorders (trisomy 18 or Down syndrome) or single gene mutation. Its worldwide prevalence is estimated to be 1-3%. The genetic etiology of non-syndromic ID is poorly understood. To date, more than 100 loci have been reported to be associated with non-syndromic ID. The objective of this study was to identify the causative genes for three.

Materials & Methods: This cross-sectional study was conducted in the Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Pakistan from March 2014 to August 2015. The inclusion criteria set for the families was consanguineous relation and more than two patients per family (including cousins). All the patients were tested individually in friendly atmosphere using IQ test to scale the ID on the basis of performance. Thereafter, blood samples were taken by aseptic method and DNA was extracted for the purpose of doing genetic analysis. In genetic analysis, exome sequencing was performed to find the pathogenic variants. Subsequently. Sanger sequencing was also done to see the segregation of pathogenic variants.

Results: Genetic analysis found mutation in AP4B1 in Family 1, in WDR62 in Family 2, while Family 3 was unremarkable.

Conclusion: The study involved genetic analysis of three consanguineous families and found mutation in AP4B1 in Family 1, in WDR62 in Family 2, while Family 3 was unremarkable. The present research will help in devising molecular diagnostic technics for pre-marital and pre-conception testing.


Intellectual disability; DNA; Genotype; Exomes; Exome sequencing; Gene clusters; Chromosome; Mutation; Chromosomal disorders; Molecular diagnostic technics.

Full Text:



McGrother C, Thorp C, Taub N, Machado O. Prevalence, disability and need in adults with severe learning disability. Tiz Learn Dis Rev 2001; 6: 4-13.

McGuigan SM, Hollins S, Attard M. Age-specific standardized mortality rates in people with learning disability. J Intellect Disabil Res 1995; 39: 527-31.

Patja K. Life expectancy of people with intellectual disability: a 35-year follow-up study. J Intellect Disabil Res 2000; 44: 590-9.

World Health Organization. International Classification of Diseases, 10th Revision. World Health Organization, Geneva; 1992.

Leonard R, Alison L. Critical incident stress debriefing and its effects on coping strategies and anger in a sample of Australian police officers involved in shooting incidents. Work & Stress 1999; 13(2):144-61.

Beirne-Smith M, Patton JR, Kim SH. Mental Retardation: An Introduction to Intellectual Disabilities. 7th ed. Harlow: Pearson; 2006.

Curry CJ, Stevenson RE, Aughton D, Byrne J, Carey JC, Cassidy S, et al. Evaluation of mental retardation: recommendations of a consensus conference. Am J of Med Genet 1997 Nov; 72(4):468-77.<468::AID-AJMG18>3.0.CO;2-P

Chelly J, Khelfaoui M, Francis F, Chérif B, Bienvenu T. Genetics and pathophysiology of mental retardation. Euro J Hum Genet 2006 Jun; 14(6):701-13.

Roeleveld N, Zielhuis GA, Gabreëls F. The prevalence of mental retardation: a critical review of recent literature. Dev Med Child Neurol 1997 Feb; 39(2):125-32.

Maulik PK, Harbour CK, McCarthy J. Epidemiology. In: Tsakanikos E, McCarthy J, editors. Handbook of Psychopathology in Intellectual Disability. New York: 2014; Springer.

Daily DK, Ardinger HH, Holmes GE. Identification and evaluation of mental retardation. Am Fam Physician 2010 Feb 15; 61(4):1059-67. Erratum in: Am Fam Physician 2000 Sep 1; 62(5):961-3.

Siderius LE, Hamel BC, van Bokhoven H, de Jager F, van den Helm B, Kremer H, et al. X-linked mental retardation associated with cleft lip/palate maps to Xp11.3-q21.3. Am J Med Genet 1999 Jul; 85 (3):216-20.<216::AID-AJMG6>3.0.CO;2-X

Laumonnier F, Holbert S, Ronce N, Faravelli F, Lenzner S, Schwartz CE, et al. Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate. J Med Genet 2005 Oct; 42 (10): 780-6.

Michael W. Malnutrition is cheating its survivors, and Africa's future. The New York Times: 2008 Dec 28; New York.

Sundaram SK, Sivaswamy L, Makki MI, Behen ME, Chugani H T. Absence of arcuate fasciculus in children with global developmental delay of unknown etiology: a diffusion tensor imaging study. J Pediatr 2008 Feb; 152 (2):250-5.doi:10.1016/j.jpeds.2007.06.037

Leonard H, Wen X. The epidemiology of mental retardation: challenges and opportunities in the new millennium. Mental Retard Dev Disabil Res Rev 2002; 8(3):117-34.

Zlotogora J. The molecular basis of autosomal recessive diseases among the Arabs and Druze in Israel. Human Genet 2010 Nov; 128(5):473-9.



  • There are currently no refbacks.

Copyright (c) 2020 Jamshed Khan, Muhammad Junaid, Shahab Uddin, Khalida Moeed, Usman Ullah, Shehla Aman

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.