[A case of rare hereditary Siddiqi syndrome with novel neuropsychiatric signs].

A fifth world case of autosomal recessive Siddiqi syndrome (SIDDIS) related to ene is presented. In a consanguineous Lezgin (a Dagestan ethnicity) family, there were two affected brothers aged 28 yrs (proband, personally examined) and 32 yrs. Whole-exome sequencing followed by familial Sanger sequencing detected a novel missence variant c.

[Developmental and epileptic encephalopathy produced by the ATP1A2 mutation].

A case of DEE98, a rare developmental and epileptic encephalopathy related to previously reported the missense mutation p.Arg908Gln in the gene, is described. A girl examined first time in 11 months had microcephaly, severe mental and motor delay, strabismus, spastic paraparesis and pachypolymicrogyria on brain MRI that is atypical for DEE98.

[Early-onset familial Alzheimer's disease with spastic paraparesis associated with PSEN1 gene].

A familial case of a rare autosomal dominant Alzheimer's disease (AD), related to gene (AD3, OMIM 607822), differing from common multifactorial form by earlier onset and, in part of cases, by accompanying neurological signs, spastic paraparesis particularly, is presented. The first sign in a female proband and in her son was paraparesis manifested at the age of 29 and 21 years, respectively. Cognitive disturbances developed soon; the former diagnosis was hereditary spastic paraplegia with cognitive impairment, In the proband examined in 2008 at 33 years old the diagnosis was not established.

[A case of spastic paraplegia with SPG4 and SPG3 associated mutations].

A rare case of autosomal dominant spastic paraplegia in a 36-year-old female with two reported earlier mutations of most common spastic paraplegia forms: SPG4 (mutation p.Cys28Leufs*20 in gene) and SPG3 (mutation p.Val405Met in gene) is presented.

[Gerstmann-Sträussler disease: a familial case with common PRNP mutation and atypical features].

Gerstmann-Sträussler disease (GSD) is a very rare autosomal dominant late-onset neurodegenerative disorder related to prion protein gene . Mutation p.Pro102Leu produces about 80% of cases, which are often named GSD-102.

Genetic and Clinical Spectrum of GNE Myopathy in Russia.

GNE myopathy (GNEM) is a rare hereditary disease, but at the same time, it is the most common distal myopathy in several countries due to a founder effect of some pathogenic variants in the gene. We collected the largest cohort of patients with GNEM from Russia and analyzed their mutational spectrum and clinical data. In our cohort, 10 novel variants were found, including 2 frameshift variants and 2 large deletions.

Complex Diagnostics of Non-Specific Intellectual Developmental Disorder.

Intellectual development disorder (IDD) is characterized by a general deficit in intellectual and adaptive functioning. In recent years, there has been a growing interest in studying the genetic structure of IDD. Of particular difficulty are patients with non-specific IDD, for whom it is impossible to establish a clinical diagnosis without complex genetic diagnostics.

[Atypical spastic paraplegia type 4 due to p.Arg499His mutation in SPAST gene].

A case of spastic paraplegia type 4 (SPG4) due to p.Arg499His mutation in a child, aged 2 years 8 months, is presented. The differences of this first Russian case with the mutation and of a number of reported cases from typical SPG4 are very early onset, severe disabling spasticity and additional signs, cognitive disturbances in particular; mutations are also infrequent.

Clinical Manifestations of Various Molecular Cytogenetic Variants of Eight Cases of "8p Inverted Duplication/Deletion Syndrome".

Inverted duplication syndrome with an adjacent terminal deletion of the short arm of chromosome 8-inv dup del(8p)-is a rare complex structural chromosomal rearrangement with a wide range of clinical manifestations. Molecular cytogenetic variants of chromosomal imbalance depend on the mechanism of rearrangement formation. We analyzed the clinical-genetic and molecular cytogenetic characteristics of the 8p inverted duplication/deletion syndrome, as well as the genotype-phenotype correlation in eight unrelated cases with the rearrangement of inv dup del(8p).

[Diversity of CACNA1A-related disorders].

Four cases of autosomal dominant CNS disorders related to mutations and detected by massive parallel sequencing are reported: a non-familial case of episodic ataxia type 2 (EA2) with the previously reported mutation c.269_270insA (p.Tyr90Ter) in a 35-year-old man; familial hemiplegic migraine type 1 (FHM1) in a girl aged 3 years 10 months and her mother aged 38 yrs with a novel mutation 1829C>T (p.

A Mosaic Mutation in the Gene in a Case of Merosin-deficient Congenital Muscular Dystrophy.

Merosine deficient congenital muscular dystrophy is one of the most common forms of congenital muscular dystrophy. This disease is caused by a primary deficiency or a functionally inactive form of the protein merosin in muscle tissue. The type of inheritance of this disease is autosomal recessive.

[Autosomal dominant spastic paraplegias].

Objective: To estimate the proportion and spectrum of infrequent autosomal dominant spastic paraplegias in a group of families with DNA-confirmed diagnosis and to investigate their molecular and clinical characteristics.

Material And Methods: Ten families with 6 AD-SPG: SPG6 (=1), SPG8 (=2), SPG9A (=1), SPG12 (=1), SPG17 (=3), SPG31 (=2) were studied using clinical, genealogical, molecular-genetic (massive parallel sequencing, spastic paraplegia panel, whole-exome sequencing, multiplex ligation-dependent amplification, Sanger sequencing) and bioinformatic methods.

Results And Conclusion: Nine heterozygous mutations were detected in 6 genes, including the common mutation p.

[AP4-assocated hereditary spastic paraplegias].

Objective: In the course of studies of spastic paraplegias in Russian patients to detect AP4-associated forms, estimate their proportion in the total SPG group and analyze clinical and molecular characteristics.

Material And Methods: Five families of Russian ethnicity: four with SPG47, one with SPG51 (4 girls and a boy aged 2.5-9 years) were studied.

Retrospective analysis of 17 patients with mitochondrial membrane protein-associated neurodegeneration diagnosed in Russia.

Introduction: Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a rare neurological syndrome caused by pathogenic variants in the C19orf12 and is characterized by iron deposition in the basal ganglia and substantia nigra. Only a limited number of cohort studies were published to date and the prevalence of MPAN remains uncertain.

Methods: Recruited subjects with MPAN in Russia were diagnosed by whole-exome sequencing or Sanger sequencing of the C19orf12 gene.

Mitochondrial DNA maintenance disorders in 102 patients from different parts of Russia: Mutational spectrum and phenotypes.

Currently, pathogenic variants in more than 25 nuclear genes, involved in mtDNA maintenance, are associated with human disorders. mtDNA maintenance disorders manifest with a wide range of phenotypes, from severe infantile-onset forms of myocerebrohepatopathy to late-onset forms of myopathies, chronic progressive external ophthalmoplegia, and parkinsonism. This study represents the results of molecular genetic analysis and phenotypes of 102 probands with mtDNA maintenance disorders.

KIF1A-related autosomal dominant spastic paraplegias (SPG30) in Russian families.

Background: Spastic paraplegia type 30 (SPG30) caused by KIF1A mutations was first reported in 2011 and was initially considered a very rare autosomal recessive (AR) form. In the last years, thanks to the development of massive parallel sequencing, SPG30 proved to be a rather common autosomal dominant (AD) form of familial or sporadic spastic paraplegia (SPG),, with a wide range of phenotypes: pure and complicated. The aim of our study is to detect AD SPG30 cases and to examine their molecular and clinical characteristics for the first time in the Russian population.

[Spastic ataxia of Charlevoix-Saguenay: the first Russian case report and literature review].

Spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare autosomal recessive neurodegenerative disease related to SACS gene and characterized by cerebellar, pyramidal and some other signs. The disease was delineated in Quebec, where it cumulates due to founder effect and has similar phenotype with very early onset. ARSACS in other populations is more variable.

[Hereditary spastic paraplegia type 4 (SPG4) in Russian patients].

Aim: To investigate molecular, clinical and genealogical characteristics of SPG4 in a first representative Russian group, to estimate SPG4 proportion among all DNA-diagnosed spastic paraplegias.

Material And Methods: Fifty unrelated Russian families with SPG4 detected in the course of clinical and molecular studies of spastic paraplegias were studied. Clinical, genealogical and several molecular methods were used, i.

HINT1 gene pathogenic variants: the most common cause of recessive hereditary motor and sensory neuropathies in Russian patients.

Pathogenic variants in the HINT1 gene lead to hereditary axonopathy with neuromyotonia. However, many studies show that neuromyotonia may remain undiagnosed, while axonopathy is the major clinical finding. The most common cause of neuromyotonia and axonopathy, especially in patients of Slavic origin, is a c.

Mutational Spectrum of Spast (Spg4) and Atl1 (Spg3a) Genes In Russian Patients With Hereditary Spastic Paraplegia.

Hereditary spastic paraplegia (HSP) comprises a heterogeneous group of neurodegenerative disorders, it share common symptom - of progressive lower spastic paraparesis. The most common autosomal dominant (AD) forms of HSP are SPG4 (SPAST gene) and SPG3 (ATL1 gene). In the current research we investigated for the first time the distribution of pathogenic mutations in SPAST and ATL1 genes within a large cohort of Russian HSP patients (122 probands; 69 famillial cases).

[Ataxia-telangiectasia with rare phenotype and unusual pedigree].

The authors present an unique familial case of ataxia-telangiectasia (AT) mimicking autosomal dominant inheritance with different phenotypes in a 3-year-old boy (ataxia and moderate dyskinesia since 1.5 years) and his 31-year-old mother (mild dystonia, predominantly torticollis, since 10 years). Exome sequencing of the boy detected two heterozygous ATM mutations c.

Ataxia with Oculomotor Apraxia Type 4 with Common "Portuguese" and Novel Mutations in Two Belarusian Families.

Ataxia with oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive, -related disorder delineated in 2015 in Portugal. We diagnosed AOA4 by next generation sequencing (NGS) followed by Sanger's sequencing in three boys from two unrelated Belarusian families. In both families, one of the heterozygous mutations was c.

[Common forms of hereditary spastic paraplegias].

A group of hereditary spastic paraplegias includes about 80 spastic paraplegia genes (SPG): forms with identified (almost 70) or only mapped (about 10) genes. Methods of next generation sequencing (NGS), along with new SPG discovering, modify knowledge about earlier delineated SPG. Clinical and genetic characteristics of common autosomal dominant (SPG4, SPG3, SPG31) and autosomal recessive (SPG11, SPG7, SPG15) forms are presented.

[Coincidence of hereditary motor and sensory neuropathy type 1A and limb girdle muscular dystrophy type 2A].

A rare case of two neuromuscular disorders in a 29-year-old female is presented: autosomal dominant hereditary motor and sensory neuropathy type 1A (HMSN1A) due to PMP22 duplication and autosomal recessive limb girdle muscular dystrophy type 2A (LGMD2A) produced by CAPN3 common mutation c.550delA and novel c.575C>G (p.