PhD in Human Skin Disorders, MPhil in Human Ectodermal Dysplasias, Master in Biochemistry Molecular Biology.
RESEARCH INTERESTS
Human Genetics, Rare Mendelian Disorders, Exome Analysis, Bioinformatics.
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Scopus Publications
Scopus Publications
The genetic spectrum of achromatopsia in consanguineous families: insights from Whole exome sequencing across 15 affected individuals Sonehra, Qaiser Zaman, Hina Gul, Najumuddin, Waqas Khan, Bilal Shaker, Gul Ghani, Mubarak Hussain, Muhammad Owais, Hammad Tufail Chaudhary, Muhammad Anas, Ihtisham ul Haq, Sabar Khan, Zohaib Khan, Fuzail Ahmad, Gauhar Rahman, Rafiq Muhammad Khan, Jamal Nasir, Musharraf Jelani Ophthalmic Genetics, 2026 Introduction Achromatopsia (ACHM) is a rare, inherited disorder in which patients cannot distinguish colors. The clinical phenotypes include light sensitivity, impaired color vision, partial or complete loss of photoreceptor function, reduced visual acuity and nystagmus. To date, six genes (CNGA3, CNGB3, GNAT2, PDE6H, PDE6C, and ATF6) are known to be the primary causes of ACHM, affecting the normal function of the cone photoreceptors.Methodology Whole-exome sequencing was performed in five families with 15 affected individuals. Candidate variants, prioritized using VARDIGS, were confirmed by Sanger sequencing and evaluated according to ACMG (2015) criteria. In-silico protein modeling and molecular dynamics simulations were employed to predict structural consequences of the variants.Results All affected individuals exhibited hallmark clinical features of congenital achromatopsia, including vision loss, photophobia, night blindness, color blindness, refractive errors (myopia/hyperopia), and nystagmus. Notably, progressive vision loss was observed in three families. Four homozygous pathogenic variants were identified: CNGA3:c.1641C > A p.(Phe547Leu), CNGB3:c.199_200delAC p.(Thr67GlnfsTer20), CNGB3:c.1214T > C p.(Leu405Ser), and PDE6C: c.1336 G > T p.(Glu446Ter), all consistent with cone dystrophies phenotypes.Conclusion Our findings expand the mutational spectrum of achromatopsia and other inherited retinal diseases. To the best of our knowledge, these variants have been reported for the first time in Pakhtun ethnic group of Pakistani population. The identification of pathogenic variants provides valuable insight for future research on gene therapy eligibility and personalized medicine.
Pathogenic variants identification in primary congenital glaucoma patients using whole exome sequencing Shahzad Ahmad, Muhammad Saleem Gandapur, Musharraf Jelani, Anees Muhammad, Ihtisham Ul Haq, Yousaf Jamal Mahsood, Sajjad Ahmad, Wadi B. Alonazi, Nousheen Bibi, Muhammad Tahir Sarwar, Taj Ali Khan Scientific Reports, 2025 Primary Congenital Glaucoma (PCG) is a severe form of glaucoma that affects infants and young children that damage and causes vision impairment. Despite being a well-known condition, the genetic basis of PCG, particularly in highly consanguineous populations like the Pashtun community, still needs to be explored. Six consanguineous Pashtun families (PCG-01, PCG-02, PCG-03, PCG-04, PCG-05, & PCG-07) suffering from PCG were recruited for whole exome sequencing. A prioritization strategy was employed to identify variants in known PCG-related genes, primarily focusing on CYP1B1. Sanger sequencing was carried out to validate candidate variants and perform segregation studies in affected individuals, siblings, parents, and controls. Whole exome sequencing revealed four pathogenic homozygous variants in six PCG families. Notably, a novel homozygous mutation, c.9delC (S4Afs9), was identified in the CYP1B1 gene in one family (PCG-07). Additionally, the previously unreported variant c.1168 C > A (p.R390S) was found in two families (PCG-2 and PCG-5). Known mutations, including c.868dupC (p. R290Pfs36) and c.1169G > A (p.R390H), were also detected in PCG-01 and PCG-04 families, respectively. Furthermore, a polymorphism, c.1294 C > G (p.L432V), was observed in family PCG-03. This study identifies novel pathogenic variants associated with PCG in consanguineous Pashtun families, highlighting the role of CYP1B1 mutations in PCG development. The findings contribute to a deeper understanding of the genetic basis of PCG and may aid in genetic counselling and early intervention strategies in affected populations.
Polymerase chain reaction and its variants in molecular diagnostics Anam Nayab, Ahmed Waqas, Musharraf Jelani, Muhammad Umair Innovations and Implications in Molecular Diagnostics, 2025 Polymerase chain reaction (PCR) has revolutionized molecular diagnostics since its invention by Kary Mullis in 1983, enabling exponential amplification of specific DNA sequences and making it possible to detect minute quantities of nucleic acids in a sample. This chapter delves into the principle of PCR, explaining its foundational steps of denaturation, annealing, and extension, which are repeated in cycles to achieve amplification. The chapter also explores the critical components required for PCR, including template DNA, primers, DNA polymerase, dNTPs, buffer solution, and magnesium ions. It further discusses various PCR variants such as real-time PCR (qPCR), Nested PCR, multiplex PCR, and touchdown PCR, each enhancing sensitivity, specificity, and range of applications in molecular diagnostics. The chapter highlights the extensive applications of these techniques in pathogen detection, genetic testing, cancer diagnostics, forensic science, and environmental and food safety. Through these advancements, PCR continues to be an indispensable tool in molecular biology and diagnostics, providing accurate and rapid detection of genetic material crucial for disease diagnosis, genetic analysis, and forensic investigations.
Whole exome sequencing in 33 patients revealed 4 novel variants in 11 limbs-girdle muscular dystrophy families Sonehra, Ishtiaq Ahmed, Fahimullah, Abdul Rahman, Ranjha Khan, Ahmed Waqas, Hammad Tufail Chaudhary, Obaid Ur Rahman, Muhammad Abbas, Nabil Tariq, Muhammad Tariq, Muhammad Asim, Gul Ghani, Muhammad Sohaib, Mansoor Khan, Bakht Tarin Khan, Taimoor Khan, Gauhar Rehman, Muhammad Umair, Musharraf Jelani, Qaiser Zaman Gene Reports, 2025
Molecular characterization of autosomal recessive Glycogen storage disease type Ib in a Pakistani family Zeeshan Nazir, Musharraf Jelani, Naveed Wasif, Fakhar Alam Khyber Medical University Journal, 2025 Objective: To investigate Glycogen storage disease GSD type Ib in a Pakistani family through whole exome sequencing (WES) and Sanger sequencing to identify the genetic mutation and confirm its autosomal recessive inheritance. Methods: This case-control and observational study was conducted at Islamia College University Peshawar, Pakistan, in the laboratory of Center for Omic Sciences in collaboration with Ulm University, Germany within a period of one year. Comprehensive clinical evaluations, comprising radiological examinations and liver function tests, established the diagnosis of GSD in the index patient, who presented with hepatomegaly, oral ulcerations, night tremors, short stature and delayed speech development as compared to her normal age controls and laboratory results indicated hypoglycemia and hyperuricemia. Whole exome sequencing (WES) was performed on the index patient to identify mutations in the SLC37A4 gene, followed by Sanger sequencing of family members to confirm the autosomal recessive inheritance of the recognized mutation. Results: It is estimated that 80% of GSD-I patients have type I-a and only 20% are affected with type I-b. The analysis revealed a previously reported alteration (c.92-94del; p.Phe31del) in the SLC37A4 gene, found in a homozygous state in the affected sibling, while obligate carriers were heterozygous. The variant was absent in fifty healthy controls from the same ethnic background. Conclusion: The study highlights the role of WES and Sanger sequencing in the diagnosis of rare diseases like GSD-Ib and recommends genetic testing of close relatives to assess carrier status and guide informed reproductive and clinical decisions in order to prevent recurrence.
A homozygous variant in ARHGAP39 is associated with lethal cerebellar vermis hypoplasia in a consanguineous Saudi family Abdulfatah M. Alayoubi, Fatima Alfadhli, Mehnaz, Alia M. Albalawi, Khushnooda Ramzan, Musharraf Jelani, Sulman Basit Scientific Reports, 2024 Cerebellar vermis hypoplasia refers to a varying degree of incomplete development of the cerebellum and vermis. A Saudi family with four affected individuals with cerebellar vermis hypoplasia, facial dysmorphology, visual impairment, skeletal, and cardiac abnormalities was ascertained in this study. Three out of four patients could not survive longer and had died in early infancy. Genetic analysis of the youngest affected was performed by genome-wide homozygosity mapping coupled with whole exome sequencing (WES), followed by Sanger validation. Genome-wide genotyping analysis mapped the phenotype to chromosome 8q24.3. Using an autosomal recessive model, considering deleterious variants with minor allele frequency of less than 0.001 in WES data, a homozygous missense variant (NM_025251.2; ARHGAP39; c.1301G > T; p.Cys434Phe) was selected as a potential candidate for the phenotype. The variant (c.1301G > T) in the ARHGAP39 is in the region of homozygosity on chromosome 8q24.3. ARHGAP39 is a Rho GTPase-activating protein 39 and has been known to regulate apoptosis, cell migration, neurogenesis, and cerebral and hippocampal dendritic spine morphology. Mice homozygous for arhgap39 knockouts have shown premature embryonic lethality. Our findings present the first ever human phenotype associated with ARHGAP39 alteration.
Unveiling genetics of non-syndromic albinism using whole exome sequencing: A comprehensive study of TYR, TYRP1, OCA2 and MC1R genes in 17 families Qaiser Zaman, Jamshid Khan, Mashal Ahmad, Hamza Khan, Hammad Tufail Chaudhary, Gauhar Rehman, Obaid Ur Rahman, Muhammad M. Shah, Javeria Hussain, Qaisar Jamal, Bakht Tareen Khan, Muhammad A. Khan, Sadeeda, Kalsoom Sahar, Muhammad Idrees, Raees Ahmad, Mohammad Shah Faisal, Muhammad Ismail Khan, Muhammad Khisroon, Angham Abdulrhman Abdulkareem, Eugene Lee, Seung Woo Ryu, Nousheen Bibi, Osama Yousef Muthaffar, Musharraf Jelani, Muhammad Imran Naseer Gene, 2024
Two novel homozygous variants of ATP6V0A2 and ALDH18A1 lead to autosomal recessive cutis laxa type 2 and 3 in two Pakistani families Qaiser Zaman, Aiman Iftikhar, Gauhar Rehman, Qadeem Khan, Najumuddin, Amin Jan, Jamshid Khan, Muhammad Anas, Laiba, Muhammad Umair, Osama Yousef Muthaffar, Angham Abdulrhman Abdulkareem, Fehmida Bibi, Muhammad Imran Naseer, Musharraf Jelani Journal of Gene Medicine, 2023 BackgroundAutosomal recessive cutis laxa type 2A (ARCL2A; OMIM: 219200) is characterized by neurovegetative, developmental and progeroid elastic skin anomalies. It is caused by biallelic variation in ATPase, H+ transporting V0 subunit A2 (ATP6V0A2; OMIM: 611716) located on chromosome 12q24.31. Autosomal recessive cutis laxa type 3A (ARCL3A; OMIM: 219150) is another subclinical type characterized by short stature, ophthalmological abnormalities and a progeria‐like appearance. The ARCL3A is caused by loss of function alterations in the aldehyde dehydrogenase 18 family member A1 (ALDH18A1; OMIM: 138250) gene located at chromosome 10q24.1.MethodsWhole‐exome sequencing (WES), and Sanger sequencing were performed for molecular diagnosis. 3D protein modeling was performed to investigate the deleterious effect of the variant on protein structure.ResultsIn this study, clinical and molecular diagnosis were performed for two families, ED‐01 and DWF‐41, which displayed hallmark features of ARCL2A and ARCL3A, respectively. Three affected individuals in the ED‐01 family (IV‐4, IV‐5 and V‐3) displayed sagging loose skin, down‐slanting palpebral fissures, excessive wrinkles on the abdomen, hands and feet, and prominent veins on the trunk. Meanwhile the affected individuals in the DWF‐41 family (V‐2 and V‐3) had progeroid skin, short stature, dysmorphology, low muscle tone, epilepsy, lordosis, scoliosis, delayed puberty and internal genitalia. WES in the index patient (ED‐01: IV‐4) identified a novel homozygous deletion (NM_012463.3: c.1977_1980del; p.[Val660LeufsTer23]) in exon 16 of the ATP6V0A2 while in DWF‐41 a novel homozygous missense variant (NM_001323413.1:c.1867G>A; p.[Asp623Asn]) in exon 15 of the ALDH18A1 was identified. Sanger validation in all available family members confirmed the autosomal recessive modes of inheritances in each family. Three dimensional in‐silico protein modeling suggested deleterious impact of the identified variants. Furthermore, these variants were assigned class 1 or “pathogenic” as per guidelines of American College of Medical Genetics 2015. Screening of ethnically matched healthy controls (n = 200 chromosomes), excluded the presence of these variations in general population.ConclusionsTo the best of our knowledge, this is the first report of ATP6V0A2 and ALDH18A1 variations in the Pakhtun ethnicity of Pakistani population. The study confirms that WES can be used as a first‐line diagnostic test in patients with cutis laxa, and provides basis for population screening and premarital testing to reduce the diseases burden in future generations.
