Shahryar Alavi

University College London | UCL · Institute of Neurology

When replication machinery reaches a nucleosome, the histone core must be evicted temporarily and then be deposited onto the newly synthesised daughter strands just behind the replication fork. In addition, as the DNA being duplicated during replication, cells need to double the number of core histones to restore their chromatin organisation proper...

Aims Mutations in PIK3CA, which encodes p110α subunit of PI3K class IA enzymes, are highly frequent in breast cancer. Here, we aimed to probe mutations in exon 9 of PIK3CA and computationally simulate their function. Materials and methods PCR/HRM and PCR/sequencing were used for mutation detection in 40 breast cancer specimens. The identified muta...

There is a large proportion of patients with neurodevelopmental disorders (NDD) remaining undiagnosed by exome sequencing. We hypothesised that this is not solely because of missing non-exonic variants or unknown disease genes, but could be due to our analysis approach.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a new gene implicated in PD and childhood neu...

A newly identified subtype of hereditary axonal motor neuropathy, characterized by early proximal limb involvement, has been discovered in a cohort of 34 individuals with biallelic variants in von Willebrand factor A domain containing 1 (VWA1). This study further delineates the disease characteristics in a cohort of 20 individuals diagnosed through...

Overview: Juvenile papillomatosis of the breast (JPB), also known as Swiss cheese disease, is a benign condition occurs in individuals with a family history of breast carcinoma and its incidence in males is rare. Here, we report a case with several affected males by JPB or gynecomastia, harbouring a significant germline mutation in the ESR1 gene. M...

Autophagy is a fundamental and evolutionary conserved biological pathway with vital roles in intracellular quality control and homeostasis. The process of autophagy involves the engulfment of intracellular targets by autophagosomes and their delivery to the lysosome for digestion and recycling. We have previously reported recessive variants in EPG5...

Charcot-Marie-Tooth Disease is a clinically and genetically heterogeneous group of hereditary neuropathies, with over 100 causative genes identified to date. Despite progress in genetic sequencing, around a quarter of patients remain unsolved. Through international collaborations, we identified 16 recessive variants in Rho GTPase activating protein...

FLVCR1 encodes Feline leukemia virus subgroup C receptor 1 (FLVCR1), a solute carrier (SLC) transporter within the Major Facilitator Superfamily. FLVCR1 is a widely expressed transmembrane protein with plasma membrane and mitochondrial isoforms implicated in heme, choline, and ethanolamine transport. While Flvcr1 knockout mice die in utero with ske...

Objectives Intronic FGF14 GAA repeat expansions have recently been found to be a common cause of hereditary ataxia (GAA- FGF14 ataxia; SCA27B). The global epidemiology and regional prevalence of this newly reported disorder remain to be established. In this study, we investigated the frequency of GAA- FGF14 ataxia in a large cohort of Brazilian pat...

MED27 is a subunit of the Mediator multiprotein complex, which is involved in transcriptional regulation. Biallelic MED27 variants have recently been suggested to be responsible for an autosomal recessive neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia. We further delineate the clinical phenotype of MED27-related d...

In the field of rare diseases, progress in molecular diagnostics led to the recognition that variants linked to autosomal-dominant neurodegenerative diseases of later onset can, in the context of biallelic inheritance, cause devastating neurodevelopmental disorders and infantile or childhood-onset neurodegeneration. TOR1A-associated arthrogryposis...

Purpose Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual develo...

Purpose: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 varian...

Biallelic pathogenic variants in the genes encoding the dolichol‐phosphate mannose synthase subunits (DPM) which produce mannosyl donors for glycosylphosphatidylinositols, N‐glycan and protein O‐ and C‐mannosylation, are rare causes of congenital disorders of glycosylation. Pathogenic variants in DPM1 and DPM2 are associated with muscle–eye–brain (...

PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated families. The individuals presented with moderate to profound deve...

PPFIBP1 encodes for the liprin-β1 protein which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster . By exome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 14 individuals from 10 unrelated families. The individuals presented with moderate to profound developmental d...

Objective: Human genomics established that pathogenic variation in diverse genes can underlie a single disorder. For example, hereditary spastic paraplegia (HSP) is associated with over 80 genes with frequently only few affected individuals described for each gene. Herein, we characterize a large cohort of individuals with biallelic variation in E...

In recent years, many strategies have been used to overcome the fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors (TKIs) resistance caused by different mutations. LY2874455 (or 6LF) is a pan-FGFR inhibitor which is identified as the most efficient TKI for all resistant mutations in FGFRs. Here, we perform a comparative dynamics st...

Background Mutations in PIK3CA, which encodes p110 subunit of PI3K class IA enzyme, are highly frequent in breast cancer. Here, we aimed to probe mutations in exon 9 of PIK3CA and computationally simulate their function. Method PCR/HRM and PCR/sequencing were used for mutation detection in 40 breast cancer specimens. The identified mutations were q...

Background Mutations in PIK3CA, which encodes p110 subunit of PI3K class IA enzyme, are highly frequent in breast cancer. Here, we aimed to probe mutations in exon 9 of PIK3CA and computationally simulate their function. Method PCR/HRM and PCR/sequencing were used for mutation detection in 40 breast cancer specimens. The identified mutations were q...

Background Mutations in PIK3CA, which encodes p110 subunit of PI3K class IA enzyme, are highly frequent in breast cancer. Here, we aimed to probe mutations in exon 9 of PIK3CA and computationally simulate their function. Method PCR/HRM and PCR/sequencing were used for mutation detection in 40 breast cancer specimens. The identified mutations were q...

قارچ کش های شیمیایی ساده ترین راه حل برای کنترل قارچ های بیماری زا پس از برداشت میوه ها و سبزی ها هستند و این درحالی است که در اکثر موارد به دلیل مشکلات زیست محیطی ناشی از بازمانده مواد شیمیایی، ایجاد سمیت برای انسان، ایجاد نژاد های مقاوم، هزینه های بسیار بالا و استفاده روز افزون از این قارچ کش ها، همواره نگرانی هایی در ارتباط با این آلودگی ها مطرح...

سرطان، یک بیماری دوران پیری است که با افزایش امید زندگی در جوامع بشری، سالانه به تعداد مبتلایان آن افزوده می‌شود. مرگ سلولی هدفمند یا آپوپتوز، یک فرآیند فعال است که طی آن سلول‌های حاوی جهش‌های گسترش دهنده‌ی سرطان حذف می‌شوند. برخی پروتئین‌های تنظیم کننده‌ی آپوپتوز، مسئولیت وارسی صحت ژنوم را به عهده دارند. پروتئین ۵۳ یکی از تعیین کنندگان اصلی آغاز ف...

پژوهش‌های اخیر نشان می‌دهند انتقال افقی ژن 16 rRNA، برخلاف انتظار، می‌تواند رخ بدهد. طبق نظریه پیچیدگی، میانکنش اجزای ریبوزوم احتمال رخداد جهش موفقیت‌آمیز در هر یک از اجزاء را بسیار کاهش می‌دهد. اخیراً گزارشی این نظریه را به چالش کشیده است و ۶۲۸ نوکلئوتید از کل 1542 نوکلئوتید 16s rRNA باکتری E. coli را به عنوان نوکلئوتیدهای تغییرپذیر معرفی کرده است...