[AP4-assocated hereditary spastic paraplegias]
Autor: | G. E. Rudenskaya, O.G. Novoselova, O.L. Mironovich, D.M. Guseva, I.F. Komar’kov, O. P. Ryzhkova, V A Kadnikova, Elena L. Dadali |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male Pediatrics medicine.medical_specialty Microcephaly Heterozygote 030105 genetics & heredity Compound heterozygosity Russia 03 medical and health sciences symbols.namesake 0302 clinical medicine medicine Humans Spasticity Child Exome sequencing Sanger sequencing business.industry Spastic Paraplegia Hereditary Homozygote medicine.disease Hypoplasia Hypotonia Pedigree Psychiatry and Mental health Phenotype Child Preschool Mutation symbols Female Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery Founder effect |
Zdroj: | Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 121(2) |
ISSN: | 1997-7298 |
Popis: | 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. Clinical and genealogical methods, whole-exome sequencing (WES) and verification by familial Sanger sequencing were used. RESULTS In our total group, including 118 families with 21 different forms, SPG AP4-associated forms accounted for 4.2% owing mainly to SPG47 (3.4%, 5th place in SPG structure; 20% and 2nd place in AE subgroup.) In non-consanguineous, unrelated SPG47 families three patients had identical genotypes: homozygosity for an earlier reported mutation c.1160_1161 delCA (p.Thr387ArgfsTer30) in AP4B1 exon 6; the 4th patient was compound-heterozygous for the same mutation and novel c.1240C>T (p.Gln414Ter) in exon 7. Frequency of c.1160_1161 delCA may be caused by founder effect in Slavic populations though the idea needs additional studies. The SPG51 patient was compound heterozygous for novel AP4E1 mutations c.2604delA (p.Ser868fs) and c.3346A>G (p.Arg1116Gly). Parent's heterozygosity in all cases was confirmed by Sanger sequencing. Phenotypes were typical: early development delay, muscle hypotony transforming into sever spasticity, mental deficiency, microceplaly (in all SPG47 cases), epilepsy (in 3 SPG47 and SPG51 cases), MRI changes, mainly hydrocephalus and/or hypoplasia of corpus callosum (in 3 SPG47 cases) and few extraneural signs. CONCLUSION AP4-associated SPG should be taken into consideration in patients with early-onset severe nervous diseases mimicking non-genetic organic CNS disorders and massive exome sequencing (WES or other variants) should be performed. |
Databáze: | OpenAIRE |
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