Assessing the Prevalence of Ectopic Cerebellar Tonsils and Accompanying Symptoms in Individuals with Various Headaches.

Objectives: Chiari malformation exhibits well-defined clinical signs, symptoms, and incidence rates in clinical studies. However, cerebellar tonsil ectopia presents with ambiguous symptoms and undetermined incidence rates in numerous studies. Our objective was to determine the incidence of cerebellar tonsil ectopia in individuals with headaches and identify additional clinical symptoms. This aims to improve diagnosis accuracy for clinicians and neurologists, leading to more effective treatment approaches. Methods: A cross-sectional study conducted in 2022 included 2305 participants aged 4-78 years presenting with headache. Chiari malformation was diagnosed using magnetic resonance imaging (MRI) scans, with a definition of cerebellar tonsil herniation extending beyond 5mm into the cervical canal. Results: The prevalence of Chiari malformation was 3.4%, with no significant gender difference (p = 0.72). There was a significant correlation between Chiari malformation and headache exacerbation due to the Valsalva maneuver (p < 0.001) and the presence of vertigo (p < 0.001). No significant association was found between Chiari malformation and accompanying symptoms such as nausea (p = 0.43), photophobia (p = 0.2), phonophobia (p = 0.52), and speech disorders (p = 0.45). Conclusion: These findings suggest a notable prevalence of Chiari malformation among headache patients and its association with specific headache characteristics, such as acute and occipital headaches, exacerbation by the Valsalva maneuver, and the co-occurrence of vertigo. These results underscore the need to consider Chiari malformation in the differential diagnosis of patients presenting with these specific headache features.

Copy number analysis from whole-exome sequencing data revealed a novel homozygous deletion in PARK7 leads to severe early-onset Parkinson's disease.

Parkinson's disease (PD), a neurodegenerative disease characterized by both motor neuron and non-motor neuron symptoms, is the most frequent neurodegenerative disease after Alzheimer's disease. Both genetic and environmental factors take part in disease etiology. Most cases are considered complex multifactorial diseases. About 15% of PD appear in the familial form, and about 5% of all cases arise from a single gene mutation. Among Mendelian causes of PD, PARK7 is one of the autosomal recessive forms due to loss-of-function mutations in both gene alleles. Both single nucleotide variants (SNVs) and copy number variations (CNVs) are observed in PARK7. This study presents an Iranian family with familial PD where some relatives had psychiatric disorders. A homozygous 1617 bp deletion in a female with early-onset PD was detected through copy-number analysis from whole-exome sequencing (WES) data in this consanguineous family. Further investigation by surveying microhomology revealed that the actual size of the deletion is 3,625 bp. This novel CNV that was in the PARK7gene is supposed to co-relation with early-onset PD and infertility in this family.

Whole-Exome Sequencing Study of Consanguineous Parkinson's Disease Families and Related Phenotypes: Report of Twelve Novel Variants.

Parkinson's disease (PD) is a common progressive neurodegenerative disorder with motor and nonmotor symptoms. Recent studies demonstrate various susceptibility loci and candidate genes for familial forms of the disease. However, the genetic basis of the familial form of early-onset PD (EOPD) is not widely studied in the Iranian population. Therefore, the present study aimed to investigate the possible causative genetic variants responsible for developing EOPD among Iranian patients. Iranian patients with a clinical diagnosis of Parkinson's disease were evaluated, and 12 consanguineous families with at least two affected individuals with early-onset PD (EOPD) were chosen to enroll in the present study. An expert neurologist group examined these families. Whole-exome sequencing (WES) was performed on PD patients, and the possible causative genetic variants related to the development of PD were reported. Exome sequencing (WES) was performed on every PD patient and revealed that patients had novel genetic variants in PRKN, PARK7, and PINK1 genes. All the genetic variants were in homozygous status and none of these variants were previously reported in the literature. Moreover, these genetic variants were "pathogenic" based on bioinformatic studies and according to the American College of Medical Genetics (ACMG). The present research revealed some novel variants for EOPD among the Iranian population. Further functional studies are warranted to confirm the pathogenicity of these novel variants and establish their clinical application for the early diagnosis of EOPD.