Mutation screening of multiple Pakistani MCPH families revealed novel and recurrent protein‐truncating mutations of ASPM. (10th December 2021)

• Record Type: Journal Article
• Authors: Hussain, Sadam; Nawaz, Amjad; Hamid, Malaika; Ullah, Waseem; Khan, Iqbal Nawaz; Afshan, Mehak; Rehman, Adil; Nawaz, Hamid; Halswick, Julia; Rehman, Shoaib‐ur; Ahmad, Sohail; Muzammal, Muhammad; Muhammad, Noor; Jan, Abid; Khan, Saadullah; Windpassinger, Christian; Khan, Muzammil Ahmad
• Is Part Of: Biotechnology and applied biochemistry. Volume 69:Number 6(2022)
• Page Start: 2296
• Page End: 2303
• Publication Date: 2021-12-10
• Subjects: ASPM mutation -- consanguinity -- genetic counseling -- Pakistani families -- primary microcephaly -- protein truncation; Biotechnology -- Periodicals; Biochemical engineering -- Periodicals; Biochemistry -- Periodicals; Biochemistry -- Periodicals; Genetic Techniques -- Periodicals; Microbiological Techniques -- Periodicals; 660.6
• DOI: 10.1002/bab.2286
• Languages: English
• ISSNs: 0885-4513

Abstract

Abstract: Autosomal primary microcephaly (MCPH) is a heterogenetic disorder that affects brain's cerebral cortex size and leads to a reduction in the cranial vault. Along with the hallmark feature of reduced head circumference, microcephalic patients also exhibit a variable degree of intellectual disability as well. Genetic studies have reported 28 MCPH genes, most of which produce microtubule‐associated proteins and are involved in cell division. Herein this study, 14 patients from seven Pashtun origin Pakistani families of primary microcephaly were analyzed. Mutation analysis was performed through targeted Sanger DNA sequencing on the basis of phenotype‐linked genetic makeup. Genetic analysis in one family found a novel pathogenic DNA change in the abnormal spindle microtubule assembly ( ASPM ) gene (NM_018136.4:c.3871dupGA), while the rest of the families revealed recurrent nonsense mutation c.3978G>A (p.Trp1326*) in the same gene. The novel reported frameshift insertion presumably truncates the protein p.(Lys1291Glyfs*14) and deletes the N‐terminus domains. Identification of novel ASPM‐truncating mutation expands the mutational spectrum of the ASPM gene, while mapping of recurrent mutation c.3978G>A (p.Trp1326*) will aid in establishing its founder effect in the Khyber Pakhtunkhwa (KPK) inhabitant population of Pakistan and should be suggestively screened for premarital counseling of MCPH susceptible families. Most of the recruited families are related to first‐degree consanguinity. Hence, all the family elders were counseled to avoid intrafamilial marriages. Abstract : Genetic Mapping Reported ASPM gene mutations in Multiple Consanguineous Pakistan Families with Primary Microcephaly