Three Iranian patients with rare subtypes of hereditary spastic paraplegia (HSP): SPG76, SPG56, and SPG69.

Some subtypes of hereditary spastic paraplegia (HSP), especially with autosomal recessive inheritance (AR-HSP), have been reported rarely. In this study, we report the clinical features and molecular results of three unrelated Iranian patients with rare subtypes of HSP, including SPG76, SPG56, and SPG69; thereafter, we compare them to other reported cases. Three patients who were clinically diagnosed with HSP and born to consanguineous parents underwent molecular assessment by whole-exome sequencing (WES), followed by Sanger sequencing and co-segregation analysis.

Atypical presentations in an RTD patient and report of novel SLC52A3 and SLC52A2 mutations.

Introduction: Riboflavin Transporter Deficiency (RTD) is a rare neurological disorder characterized by pontobulbar palsy, hearing loss, and motor cranial nerve involvement. SLC52A3 and SLC52A2 mutations are causes of RTD. SLC52A2 mutations are usually found in childhood onset cases.

JAM2 variants can be more common in primary familial brain calcification (PFBC) cases than those appear; may be due to a founder mutation.

Introduction: Mutations in JAM2 have been linked to ~ 2% of primary familial brain calcification (PFBC) cases. PFBC is a rare neurological disorder characterized by excessive calcium deposition in the brain. It causes movement disorders and psychiatric problems.

Copy Number Variations in Hereditary Spastic Paraplegia-Related Genes: Evaluation of an Iranian Hereditary Spastic Paraplegia Cohort and Literature Review.

Introduction: In human genetic disorders, copy number variations (CNVs) are considered a considerable underlying cause. CNVs are generally detected by array-based methods but can also be discovered by read-depth analysis of whole-exome sequencing (WES) data. We performed WES-based CNV identification in a cohort of 35 Iranian families with hereditary spastic paraplegia (HSP) patients.

Description of Phenotypic Heterogeneity in a -Related Family and Literature Review.

Introduction: Homozygous and compound heterozygous variants in , the gene encoding connexin-47 protein, cause Pelizaeus-Merzbacher-like disease type 1 or hypomyelinating leukodystrophy 2 (HLD2), a severe infantile-onset hypomyelinating leukodystrophy, and rarely some milder phenotypes like hereditary spastic paraplegia (HSP) type 44 (SPG44) and subclinical leukodystrophy. Herein, we report an Iranian -related family with intrafamilial phenotypic heterogeneity and review the literatures.

Methods: Whole-exome sequencing was performed for an Iranian proband, who was initially diagnosed as HSP case.

A new genetic variant, presenting as young onset rapidly progressive dementia and parkinsonism.

There are various neurodegenerative or hereditary causes of Parkinsonism. Therefore, clinicians should consider an increasing range of differential diagnoses when facing a patient with Parkinsonism, especially when associated with additional clinical features. Young-onset Parkinsonism, especially when accompanied by features uncommon in idiopathic Parkinson's disease raises the possibility of genetic etiology.

A case report of concurrent occurrence of two inherited axonopathies within a family: the benefit of whole-exome sequencing.

Mutations in and lead to the development of spastic paraplegia-18 (SPG18) and Charcot-Marie-Tooth type-2A (CMT2A), respectively. These disorders are unified by the fact that both can be termed inherited axonopathies. With whole-exome sequencing (WES), more patients of neurological disorders with clinical overlaps receive a genetic result than ever before.

White matter abnormalities in 15 subjects with SPG76.

Background And Objectives: Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders characterized by progressive pyramidal tract involvement. SPG76 is a recently identified form of HSP, caused by biallelic calpain-1 (CAPN1) variants. The most frequently described MRI abnormality in SPG76 is mild cerebellar atrophy and non-specific white matter abnormalities were reported in only one case.

The first reports of FA2H-associated neurodegeneration from two unrelated Iranian families.

Background: NBIA (neurodegeneration with brain iron accumulation) is a diverse collection of neurodegenerative illnesses defined by iron accumulation in the basal ganglia. The fatty acid hydroxylase-associated neurodegeneration, or FAHN, is one of the uncommon subtypes of NBIAs, associated with inherited autosomal recessive mutations in gene coding the membrane-bound fatty acid 2 hydroxylase (FA2H) enzyme.

Cases: Here, we report two cases with FAHN from two unrelated families from Iran confirmed by whole exome sequencing.

NMNAT1 and hereditary spastic paraplegia (HSP): expanding the phenotypic spectrum of NMNAT1 variants.

In the NAD biosynthetic network, the nicotinamide mononucleotide adenylyltransferase (NMNAT) enzyme fuels NAD as a co-substrate for a group of enzymes. Mutations in the nuclear-specific isoform, NMNAT1, have been extensively reported as the cause of Leber congenital amaurosis-type 9 (LCA9). However, there are no reports of NMNAT1 mutations causing neurological disorders by disrupting the maintenance of physiological NAD homeostasis in other types of neurons.

Potential role of FKBP5 single-nucleotide polymorphisms in functional seizures.

Objective: We investigated the associations between FKBP5 single-nucleotide polymorphisms (SNPs) and functional seizures (FS).

Methods: Seventy patients with FS, 140 with major depressive disorder (MDD), and 140 healthy controls were studied. Their DNAs were analyzed for the rs1360780 in the 3' region and rs9470080 in the 5' region of the FKBP5.

Intellectual disability associated with craniofacial dysmorphism due to POLR3B mutation and defect in spliceosomal machinery.

Background: Intellectual disability (ID) is a clinically important disease and a most prevalent neurodevelopmental disorder. The etiology and pathogenesis of ID are poorly recognized. Exome sequencing revealed a homozygous missense mutation in the POLR3B gene in a consanguineous family with three Intellectual disability with craniofacial anomalies patients.

Identification of let-7f and miR-338 as plasma-based biomarkers for sporadic amyotrophic lateral sclerosis using meta-analysis and empirical validation.

Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that in most cases occurs sporadic (sALS). The disease is not curable, and its pathogenesis mechanisms are not well understood yet. Given the intricacy of underlying molecular interactions and heterogeneity of ALS, the discovery of molecules contributing to disease onset and progression will open a new avenue for advancement in early diagnosis and therapeutic intervention.

The second family affected with a PRDM8-related disease.

Introduction: Lafora disease (LD) is a severe form of progressive myoclonus epilepsy characterized by generalized seizures, myoclonus, intellectual decline, ataxia, spasticity, dysarthria, visual loss, and in later stages, psychosis and dementia. To date, mutations in the EPM2A and EPM2B/NHLRC1 genes have been identified as the common causes of LD. However, a mutation in PRDM8 has been reported only once in a Pakistani family affected with early-onset Lafora disease.

Clinical and genetic spectrum of a large cohort of patients with δ-sarcoglycan muscular dystrophy.

Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease's severity.

Anticipation Can Be More Common in Hereditary Spastic Paraplegia with Mutations Than It Appears.

Background And Objective: Hereditary spastic paraplegia (HSP) is a heterogeneous neurodegenerative disorder with lower-limb spasticity and weakness. Different patterns of inheritance have been identified in HSP. Most autosomal-dominant HSPs (AD-HSPs) are associated with mutations of the gene (SPG4), leading to a pure form of HSP with variable age-at-onset (AAO).

Neurodegeneration with Brain Iron Accumulation and a Brief Report of the Disease in Iran.

Neurodegeneration with brain iron accumulation (NBIA) is a term used for a group of hereditary neurological disorders with abnormal accumulation of iron in basal ganglia. It is clinically and genetically heterogeneous with symptoms such as dystonia, dysarthria, Parkinsonism, intellectual disability, and spasticity. The age at onset and rate of progression are variable among individuals.