RESUMEN
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.110G>C (p.Arg37Pro) pathogenic variant in homozygous or compound heterozygous state. In this study, we analyzed a peripheral neuropathy caused by pathogenic variants in the HINT1 gene and evaluated its contribution to the hereditary neuropathy structure. The studied group included 1596 non-related families diagnosed with hereditary motor and sensory neuropathy (HMSN). The results show that HINT1 gene pathogenic variants make a significant contribution to the hereditary neuropathy epidemiology in Russian patients. They account for at least 1.9% of all HMSN cases and 9% of axonopathy cases. The most common HINT1 pathogenic variant in Russian patients is the c.110G>C (p.Arg37Pro) substitution. Its allelic frequency is 0.2% (95% CI 0.19-0.21%), carrier frequency is 1 in 250 people in Russian Federation, and the estimated disease incidence is 1 in 234,000 individuals. It was determined that the cause of this pathogenic variant's prevalence is the founder effect.
Asunto(s)
Genes Recesivos , Neuropatía Hereditaria Motora y Sensorial/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Frecuencia de los Genes/genética , Haplotipos/genética , Neuropatía Hereditaria Motora y Sensorial/epidemiología , Heterocigoto , Humanos , Desequilibrio de Ligamiento/genética , Repeticiones de Microsatélite/genética , Federación de RusiaAsunto(s)
Displasia Ectodermal Anhidrótica Tipo 1/genética , Mutación , Empalme del ARN , Femenino , Humanos , Masculino , Linaje , Federación de RusiaRESUMEN
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.Thr192Ser).Walking difficulties appeared in 27 years, the patient had signs of both disorders, more of LGMD, but was not disabled. HMSN1A was inherited from her father whose disease was not recognized earlier.
Asunto(s)
Neuropatía Hereditaria Motora y Sensorial , Distrofia Muscular de Cinturas , Adulto , Calpaína/genética , Femenino , Neuropatía Hereditaria Motora y Sensorial/diagnóstico , Neuropatía Hereditaria Motora y Sensorial/genética , Humanos , Proteínas Musculares/genética , Distrofia Muscular de Cinturas/diagnóstico , Distrofia Muscular de Cinturas/genética , MutaciónRESUMEN
OBJECTIVE: To study clinical/genetic characteristics of congenital muscular dystrophy caused by mutations in the LMNA gene in 5 patients from the Russian population. MATERIAL AND METHODS: DNA samples of 42 probands, aged from 2 months to 9 years, with characteristic signs of congenital muscular dystrophy from nonrelated families were studied. The diagnosis was based on the results of genealogical analysis, neurological examination, serum creatine phosphokinase activity, results of electroneuromyography. RESULTS AND CONCLUSION: In the Russian population, the frequency of congenital muscular dystrophy caused by mutations in the LMNA gene is not less than 12% of all cases of this group of diseases. The results indicate the presence of major mutation c.94_96delAAC in the LMNA gene. Specific phenotypic features of this form of congenital muscular dystrophy with symptoms of progressive flaccid paralysis with predominant lesions of axial muscles and plantar flexor muscles of the foot are described.
Asunto(s)
Lamina Tipo A/genética , Distrofia Muscular de Cinturas/diagnóstico , Distrofia Muscular de Cinturas/genética , Niño , Preescolar , Creatina Quinasa/sangre , Análisis Mutacional de ADN , Electromiografía , Femenino , Humanos , Lactante , Masculino , Distrofia Muscular de Cinturas/sangre , Mutación , Federación de RusiaRESUMEN
Data of own researches and the review of the literary data for studying pathogenesis and features of HMSN, type 1 Х caused by mutations in gene GJB1 are presented in this paper. X-linked HMSN is the genetic variant second for frequency in Russian, it constitute 22% from total of patients of this group. Features of this genetic variant are considerable distinction in weight clinical displays at patients man's and female. It is shown that at the majority of female patients clinical displays are expressed less, and at 20% were absent at all. The assumption is come out that at indicators of CNV from 35 to 52 m/s, it is necessary to conduct research in gene GJB1 especially at patients of a female and as to carry out search of mutations at all relatives with HMSN, type 1 X even in the absence of complaints from their party.
Asunto(s)
Enfermedad de Charcot-Marie-Tooth/diagnóstico , Enfermedad de Charcot-Marie-Tooth/genética , Conexinas/genética , Adolescente , Adulto , Enfermedad de Charcot-Marie-Tooth/epidemiología , Niño , Conexinas/química , Femenino , Frecuencia de los Genes , Humanos , Masculino , Mutación , Linaje , Estructura Terciaria de Proteína/genética , Factores Sexuales , Adulto Joven , Proteína beta1 de Unión ComunicanteRESUMEN
Hereditary motor-sensor neuropathy (HMSN) caused by mutations in the MPZ (P0) gene is a rare variant of hereditary demyelinating polyneuropathies that makes up 5-10% of all cases in different populations. Based on the complex examination of patients of the Russian Federation with different MPZ (P0) mutations, we obtained clinical-genetic, electromyographic and molecular-genetic characteristics of HMSN caused by mutations in the MPZ (P0) gene. Peculiarities of clinical presentations in patients with HMSN, types 1B and 2I, are presented. Diagnostic criteria of these genetic variants have been formed. The new allelic variants of HMSN caused by mutations in the MPZ (P0) gene are described. The distribution of mutations by protein domains has been analyzed.