Article
Genetics & Heredity
Francesca Andreoni, Claudia Sgattoni, Daniela Bencardino, Oriana Simonetti, Antonino Forabosco, Mauro Magnani
Summary: The study identified variants in the EDA, EDAR, and EDARADD genes related to HED and tooth agenesis in two families. A novel missense variant in EDAR was found to cause autosomal dominant HED, while a previously described genetic variant in EDA confirmed its role in X-linked HED. The findings highlight variable expressions of HED in heterozygous females and different modes of inheritance related to tooth development.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Francesca Andreoni, Claudia Sgattoni, Daniela Bencardino, Oriana Simonetti, Antonino Forabosco, Mauro Magnani
Summary: The study identified a novel missense variant in the EDAR gene leading to autosomal dominant HED in one family, while the previously described genetic variant in the EDA gene confirmed its role in X-linked HED in another family. The inheritance model of the missense mutation showed different relationships with X-linked HED and non-syndromic tooth agenesis.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Hoda A. Ahmed, Ghada Y. El-Kamah, Eman Rabie, Mostafa Mostafa, Maha R. Abouzaid, Nehal F. Hassib, Mennat Mehrez, Mohamed A. Abdel-Kader, Yasmine H. Mohsen, Suher K. Zada, Khalda S. Amr, Inas S. M. Sayed
Summary: Ectodermal dysplasia (ED) is a group of genetic disorders affecting structures derived from the ectoderm, with the most common phenotype being hypohidrotic/anhidrotic ectodermal dysplasia (HED) characterized by sparse hair, lack of sweat glands, and missing teeth. Molecular diagnosis is crucial for disease management, and the use of targeted next generation sequencing has allowed for the identification of genetic heterogeneity, variable expressivity, and intrafamilial phenotypic variability in ED patients.
Article
Pediatrics
Victoria-Eugenia Garcia-Martinez, Ximo Galiana-Valles, Otilia Zomeno-Alcala, Raquel Rodriguez-Lopez, Carmen Llena, Maria del Carmen Martinez-Romero, Encarna Guillen-Navarro
Summary: This article describes an 11-year-old Chinese boy with oligodontia, characterized by conical-shaped teeth as the main phenotype and other mild ectodermal signs. Genetic analysis revealed compound heterozygous pathogenic variants in the WNT10A gene and a homozygous polymorphism in the EDAR gene. The findings suggest that WNT10A mutations are primarily responsible for the dental phenotype, while the EDAR polymorphism may attenuate the severity of other ectodermal signs.
Article
Dermatology
Nobuyuki Asano, Shuichiro Yasuno, Ryota Hayashi, Yutaka Shimomura
Summary: This study identified that certain mutations in the EDARADD gene can lead to reduced NF-κB activity and exert dominant negative effects, providing insights into the molecular mechanisms underlying the disease.
JOURNAL OF DERMATOLOGY
(2021)
Article
Genetics & Heredity
Yupei Wang, Chuan Zhang, Bingbo Zhou, Ling Hui, Lei Zheng, Xue Chen, Shifan Wang, Lan Yang, Shengju Hao, Qinghua Zhang
Summary: This study identified three variations in the EDA gene, all affecting the structure of exon 1. Experimental analysis of a splicing variant (c.396 + 1 G > C) showed that it leads to a prolonged EDA-A1 transcript in vitro. Additionally, chromosomal microarray analysis confirmed a novel deletion variant in exon 1.
FRONTIERS IN GENETICS
(2022)
Article
Dentistry, Oral Surgery & Medicine
Y. Zeng, E. Baugh, S. Akyalcin, A. Letra
Summary: Mutations in WNT10A gene have been frequently associated with tooth agenesis, with most of the variants related to this condition affecting protein function and leading to decreased WNT signaling.
JOURNAL OF DENTAL RESEARCH
(2021)
Article
Health Care Sciences & Services
Kuan-Yu Chu, Yin-Lin Wang, Yu-Ren Chou, Jung-Tsu Chen, Yi-Ping Wang, James P. Simmer, Jan C. -C. Hu, Shih-Kai Wang
Summary: Familial tooth agenesis, caused by mutations in genes involved in WNT/beta-catenin signaling, is a common craniofacial anomaly in humans. This study identified pathogenic mutations in the LRP6 gene contributing to FTA and suggested that mutations in LRP6, especially in combination with WNT10A variants, may lead to more severe phenotypes.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Dermatology
Sasagu Yagi, Shuichiro Yasuno, Osamu Ansai, Ryota Hayashi, Yutaka Shimomura
Summary: Hypohidrotic ectodermal dysplasia is a rare condition characterized by reduced sweating, missing teeth, and sparse hair. In this study, in vitro experiments revealed that the degree of loss-of-function varied among different mutant EDAR proteins associated with autosomal forms, which may be correlated with the severity of the disease.
JOURNAL OF DERMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Kuan-Yu Chu, Yin-Lin Wang, Jung-Tsu Chen, Chia-Hui Lin, Chung-Chen Jane Yao, Yi-Jane Chen, Huan-Wen Chen, James P. Simmer, Jan C. -C. Hu, Shih-Kai Wang
Summary: Familial tooth agenesis (FTA) is a common craniofacial anomaly in humans. Loss-of-function mutations in PAX9 and WNT10A cause FTA, and the presence of both mutations leads to more severe phenotypes due to mutational synergism. This study identified new disease-causing mutations in PAX9 and expanded the knowledge of phenotypic and genotypic spectrums of PAX9-associated disorders, providing insights into the molecular mechanism of FTA variable expressivity.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Letter
Allergy
Bhavi P. Modi, Kate L. Del Bel, Susan Lin, Mehul Sharma, Phillip A. Richmond, Clara D. M. van Karnebeek, Edmond S. Chan, Vishal Avinashi, Wingfield E. Rehmus, Catherine M. Biggs, Wyeth W. Wasserman, Stuart E. Turvey
Summary: This study presents a family with X-linked hypohidrotic ectodermal dysplasia (XLHED), showing variable expressivity of symptoms among affected siblings. Exome sequencing identified a pathogenic nonsense variant in the EDA gene, leading to a precise molecular diagnosis of XLHED and allowing for exclusion of other differential diagnoses.
ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY
(2021)
Review
Genetics & Heredity
Yanzi Gao, Xiaohui Jiang, Zhi Wei, Hu Long, Wenli Lai
Summary: Non-syndromic tooth agenesis (NSTA) is a common dental developmental malformation affected by genetic factors. The EDA, EDAR, and EDARADD genes in the EDA/EDAR/NF-κB signaling pathway have been found to play essential roles in the pathogenesis of NSTA. This review provides an overview of the genetic basis of NSTA and highlights the importance of genetic analysis in diagnosing and managing NSTA and related ectodermal disorders.
FRONTIERS IN GENETICS
(2023)
Article
Dentistry, Oral Surgery & Medicine
Marija Zivkovic, Neda Stefanovie, Branislav Glisic, Gavrilo Brajovic, Biljana Milicic, Marija Kostic, Branka Popovic
Summary: The study aimed to investigate the prevalence of WNT10A and RUNX2 gene mutations in non-syndromic tooth agenesis and assess their potential impact on the phenotype. There was a higher prevalence of hypodontia and oligodontia, with a higher frequency of missing teeth in females. Common mutations include p.Phe228Ile, p.Arg113Cys, p.Asp217Asn, p.Gly165Arg, and others.
EUROPEAN JOURNAL OF ORAL SCIENCES
(2022)
Article
Genetics & Heredity
Xingyu Liu, Yuming Zhao, Junxia Zhu
Summary: A novel mutation (c.593G > A, p. Gly198Glu) in the collagen domain of EDA was identified, which impairs the receptor-binding activity of EDA and the transcriptional activity of NF-kappa B, leading to HED.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Dentistry, Oral Surgery & Medicine
Peter Bielik, Ondrej Bonczek, Premysl Krejci, Tomas Zeman, Lydie Izakovicova-Holla, Jana Soukalova, Jiri Vanek, Borivoj Vojtesek, Jan Lochman, Vladimir J. Balcar, Omar Sery
Summary: This study analyzed WNT10A variants in young subjects with various forms of tooth agenesis and self-reported family history of cancer. The study found that WNT10A variants significantly affect dental phenotype but no relationship between the presence of WNT10A variants and a risk of cancer was found.
CLINICAL ORAL INVESTIGATIONS
(2022)
Article
Medical Laboratory Technology
Fozia Fozia, Khadim Shah, Rubina Nazli, Sher Alam Khan, Ijaz Ahmad, Noor Mohammad, Saadullah Khan, Amal Alotaibi
Summary: Woodhouse-Sakati syndrome is a rare autosomal recessive disease with endocrine and neuroectodermal abnormalities. A consanguineous pedigree with multiple affected individuals was studied, and a splicing-site deletion in the DCAF17 gene was identified as the genetic change underlying the disease. The variant is predicted to cause exon skipping and lead to the typical phenotypic features of the syndrome in affected family members.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Biochemistry & Molecular Biology
Roquyya Gul, Muhammad Umair Hanif, Faiza Gul, Hafiz Muzzammel Rehman, Mahjabeen Saleem, Muhammad Sarfaraz Ahmad, Muhammad Usman Mirza
Summary: This study focuses on the molecular cloning, expression, and structural characterization of growth hormone-receptor (GHR) and its extracellular domain as growth hormone binding protein (GHBP) in the liver of Nili-Ravi buffalo. The research provides sequence characterization of BbGHR in Nili-Ravi buffaloes and explores the molecular interactions between growth hormone and its receptor, as well as the stability of the proteins.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Immunology
Syed Zawar Shah, Basit Jabbar, Muhammad Usman Mirza, Muhammad Waqas, Shahkaar Aziz, Sobia Ahsan Halim, Amjad Ali, Shazia Rafique, Muhammad Idrees, Asaad Khalid, Ashraf N. Abdalla, Ajmal Khan, Ahmed Al-Harrasi
Summary: Crimean-Congo haemorrhagic fever (CCHF), caused by CCHFV, is an important disease worldwide. This study designed a multi-epitope vaccine using an immunoinformatics-based approach to target CCHFV (Asia-1 genotype). Molecular docking and dynamics simulation showed that the constructed vaccine has stable and favorable interactions with Toll-like receptors, and can elicit innate, adaptive, and humoral immune responses.
Article
Immunology
Hafiz Muzzammel Rehman, Muhammad Sajjad, Muhammad Akhtar Ali, Roquyya Gul, Muhammad Irfan, Muhammad Naveed, Munir Ahmad Bhinder, Muhammad Usman Ghani, Nadia Hussain, Amira S. A. Said, Amal H. I. Al Haddad, Mahjabeen Saleem
Summary: Zika virus (ZIKV) pandemic has posed serious threats to global health, and the search for effective drugs against the viral infection is urgent. Using in silico drug exploration, three potential drug molecules were identified as potent inhibitors of Zika NS2B-NS3 protease.
Article
Dermatology
Niamatullah Khan, Khadim Shah, Fozia Fozia, Sher A. A. Khan, Nazif Muhammad, Abdul Nasir, Ijaz Ahmad, Zia U. U. Rehman, Abid Jan, Noor Muhammad, Saadullah Khan
Summary: This study identifies different sequence variants involved in different forms of hereditary ichthyosis, including a novel duplication sequence variant in the FLG gene and a previously reported nonsense sequence variant in the TGM1 gene. It also reveals a complete gene deletion in the STS gene in X-linked recessive ichthyosis. These findings have implications for genetic counseling of affected families.
INTERNATIONAL JOURNAL OF DERMATOLOGY
(2023)
Article
Genetics & Heredity
Hamed Nawaz, Mujahid, Sher Alam Khan, Farhana Bibi, Ahmed Waqas, Abdul Bari, Fardous, Niamatullah Khan, Nazif Muhammad, Amjad Khan, Sohail Aziz Paracha, Qamre M. Alam, Mohammad Azhar Kamal, Misbahuddin Rafeeq, Noor Muhammad, Fayaz Ul Haq, Shazia Khan, Arif Mahmood, Saadullah Khan, Muhammad Umair
Summary: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with diverse clinical and genetic features. This study identified novel and recurrent gene variants in Pakistani families with BBS, expanding the mutation and phenotypic spectrum of ciliopathies causing BBS. These findings highlight the importance of these genes in the development of multi-systemic human genetic disorders.
Article
Clinical Neurology
Nazif Muhammad, Syeda Iqra Hussain, Zia Ur Rehman, Sher Alam Khan, Samin Jan, Niamatullah Khan, Muhammad Muzammal, Sumra Wajid Abbasi, Naseebullah Kakar, Zia Ur Rehman, Muzammil Ahmad Khan, Muhammad Usman Mirza, Noor Muhammad, Saadullah Khan, Naveed Wasif
Summary: This study conducted a genetic analysis on two consanguineous Pakistani families and identified two novel mutations in the NSUN2 gene, which may be associated with intellectual disability. Molecular dynamic simulations were used to explore the impact of the NSUN2 missense variant on its function.
FRONTIERS IN NEUROLOGY
(2023)
Article
Pharmacology & Pharmacy
Sarfraz Ahmad, Muhammad Usman Mirza, John F. Trant
Summary: Peptide-based therapeutics are gaining attention in biomedicine due to their high specificity and low toxicity. This study provides a dataset of all di-, tri-, tetra-, and penta-peptide sequences for screening against protein targets. Access to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery campaigns.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2023)
Article
Genetics & Heredity
Asia Parveen, Muhammad Tariq, Sher Alam Khan, Naseebullah Kakar, Amina Arif, Naveed Wasif
Summary: Split-hand/foot malformation (SHFM) is a condition that exhibits diverse heterogeneity and shows reduced penetrance and variable expressivity. This study aimed to identify the genetic cause of SHFM in a family. Exome sequencing followed by Sanger sequencing revealed a novel heterozygous variant (NC_000019.9 (NM_005499.3):c.1118del) in UBA2 that cosegregated in an autosomal dominant manner in the family. Our findings highlight the unusual features of reduced penetrance and variable expressivity in SHFM.
HUMAN GENOME VARIATION
(2023)
Article
Genetics & Heredity
Rasha M. Elhossini, Inas M. Sayed, Usama Saad Hellal, Sarah A. M. Mahmoud, Mona S. Aglan, Nehal F. Hassib, Mohamed S. Abdel-Hamid
Summary: This study describes the first inherited KCNK4 variant in an Egyptian boy and his mother. The patient presented with the full-blown syndrome while the mother only exhibited some phenotypic features. Dental management resulted in significant improvement in the patient's condition.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Clinical Neurology
Syeda Iqra Hussain, Nazif Muhammad, Salah Ud Din Shah, Fardous Fardous, Sher Alam Khan, Niamatullah Khan, Adil U. Rehman, Mehwish Siddique, Shoukat Ali Wasan, Rooh Niaz, Hafiz Ullah, Niamat Khan, Noor Muhammad, Muhammad Usman Mirza, Naveed Wasif, Saadullah Khan
Summary: Intellectual disability is a condition that varies widely and is associated with mutations in the SLC13A3 and SLC9A6 genes.
Article
Biotechnology & Applied Microbiology
Syeda Iqra Hussain, Nazif Muhammad, Niamatullah Khan, Mobeen Khan, Fardous Fardous, Raheel Tahir, Muhammad Yasin, Sher Alam Khan, Shamim Saleha, Noor Muhammad, Naveed Wasif, Saadullah Khan
Summary: In this study, disease-causing variants related to intellectual disability were identified in two families through exome sequencing. One family had a variant in the CREBBP gene, while the other family had a variant in the TANGO2 gene. These findings contribute to our understanding of these disorders. Further research is needed to determine the genotype-phenotype associations.
JOURNAL OF GENE MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Saira Naseem, Samra Khan, Safdar Hussain, Muhammad Usman Mirza, Muhammad Ashraf, Zahid Shafiq, John F. Trant
Summary: This study describes the design and synthesis of xanthene-based thiosemicarbazones that show effective inhibition of acetylcholinesterase (AChE) associated with Alzheimer's Disease. These compounds demonstrate selectivity for AChE over butyrylcholinesterase (BChE) and can serve as preliminary hits for further development. Molecular docking analysis reveals the importance of the xanthene scaffold for AChE binding and the aryl R2 moiety for BChE interactions. Some compounds also show dual enzyme targeting, suggesting their potential as monotherapies for cholinesterase-related neurodegenerative diseases like Alzheimer's Disease.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)