OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with hereditary spastic paraplegia type 30 (HSP30). METHODS: A proband presented at the Second Hospital of Shanxi Medical University in August 2021 was selected as the study subject. The proband was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The proband was found to have harbored a heterozygous c.110T>C variant in exon 3 of the KIF1A gene, which can cause substitution of isoleucine by threonine at position 37 (p.I37T) and alter the function of its protein product. The same variant was not found in his parents, elder brother and elder sister, suggesting that it has a de novo origin. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PM2_Supporting+PP3+PS2). CONCLUSION The c.110T>C variant of the KIF1A gene probably underlay the HSP30 in the proband. Above finding has enable genetic counseling for this family.
Humans ; Male ; East Asian People ; Kinesins/genetics* ; Mutation ; Pedigree ; Spastic Paraplegia, Hereditary/genetics* ; Female

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics of a child with Hereditary spastic paraplegia (HSP). METHODS: A child with HSP who was admitted to the Third Affiliated Hospital of Zhengzhou University on August 10, 2020 due to discovery of tiptoeing for 2 years was selected as the study subject, and relevant clinical data was collected. Peripheral blood samples of the child and her parents were collected for the extraction of genomic DNA. And trio-whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing. Bioinformatic software was used to analyze the conservation of variant sites. RESULTS: The child was a 2-year-and-10-month-old female with clinical manifestations including increased muscle tone of lower limbs, pointed feet, and cognitive language delay. Trio-WES results showed that she had harbored compound heterozygous variants of c.865C>T (p.Gln289*) and c.1126G>A (p.Glu376Lys) of the CYP2U1 gene. And the corresponding amino acid for c.1126G>A (p.Glu376Lys) is highly conserved among various species. Based on guidelines from the American College of Medical Genetics and Genomics, the c.865C>T was predicted as a pathogenic variant (PVS1+PM2_Supporting), and c.1126G>A was rated as a variant of uncertain significance (PM2_Supporting+PM3+PP3). CONCLUSION The child was diagnosed with HSP type 56 due to compound variants of the CYP2U1 gene. Above findings have enriched the mutation spectrum of the CYP2U1 gene.
Female ; Humans ; Cytochrome P450 Family 2/genetics* ; Mutation ; Pedigree ; Phenotype ; Spastic Paraplegia, Hereditary/genetics* ; Infant

OBJECTIVE: To explore the genetic basis for a pedigree affected with hereditary spastic paraplegia type 4 (HSP4). METHODS: Peripheral venous blood samples were taken from members of the four-generation pedigree and 50 healthy controls for the extraction of genomic DNA. Genes associated with peripheral neuropathy and hereditary spastic paraplegia were captured and subjected to targeted capture and next-generation sequencing. The results were confirmed by Sanger sequencing. RESULTS: DNA sequencing suggested that the proband has carried a heterozygous c.1196C>G variant in exon 9 of the SPAST gene, which can cause substitution of serine by threonine at position 399 (p.Ser399Trp) and lead to change in the protein function. The same variant was also detected in other patients from the pedigree but not among unaffected individuals or the 50 healthy controls. Based on the ACMG 2015 guidelines, the variant was predicted to be possibly pathogenic. CONCLUSION The c.1196C>G variant of the SPAST gene probably underlay the HSP4 in this pedigree.
Base Sequence ; Humans ; Mutation ; Paraplegia/genetics* ; Pedigree ; Sequence Analysis, DNA ; Spastic Paraplegia, Hereditary/genetics* ; Spastin/genetics*

OBJECTIVE: To identify pathogenic mutation in a Chinese family affected with hereditary spastic paraplegia (HSP) through genetic testing and a follow-up survey. METHODS: Whole exome sequencing was performed on DNA samples of two patients and one unaffected member to screen candidate mutations. Sanger sequencing was used to validate the suspected mutations in all ten family members. RESULTS: Four patients and three asymptomatic members (under 25 years old) carried a c.1771T>C mutation of the KIAA0196, while the other three asymptomatic members (over 40 years old) did not carry the mutation. The mutation was predicted to be "affect protein function", "probably damaging" and "disease causing" by SIFT, PolyPhen-2 and Mutation Taster, respectively. Three asymptomatic carriers were followed up and one of them developed HSP one year later, while the other two had no signs of the disease yet. CONCLUSION The clinical phenotype of the c.1771T>C mutation of KIAA0196 has a considerable heterogeneity and this mutation may be a common pathogenic site of KIAA0196 mutations among Chinese patients with hereditary spastic paraplegia.
Adult ; Asian Continental Ancestry Group ; Heterozygote ; Humans ; Mutation ; Pedigree ; Phenotype ; Proteins ; genetics ; Spastic Paraplegia, Hereditary ; genetics

OBJECTIVE: To detect pathogenic variation in a pedigree affected with hereditary spastic paraplegia type 31 and explore its molecular pathogenesis. METHODS: Customized Roche NimbleGen capture probes were used to capture all exons of the target genes in relation with hereditary spastic paraplegia. The DNA samples were also assayed with fluorescent quantitative PCR as well as chromosomal microarray analysis using CytoScan HD chip. RESULTS: The proband and her father and grandfather were found to carry a deletion for position 85 992 693-86 842 693 on chromosome 2, which spanned approximately 900 kb and encompassed the REEP1 gene. The latter has been specifically associated with hereditary spastic paraplegia type 31. The same deletion was not found in her mother who is phenotypically normal. CONCLUSION The deletional variation of the REEP1 gene probably underlies the disease in this pedigree.
Female ; Humans ; Membrane Transport Proteins ; supply & distribution ; Paraplegia ; Pedigree ; Sequence Deletion ; Spastic Paraplegia, Hereditary ; genetics

This article reports the clinical features and C12orf65 gene mutations of a girl with autosomal recessive spastic paraplegia-55. The 8-year-old girl experienced disease onset at the age of 5 years and had optic atrophy as the main clinical manifestation, with slow movements in standing up and a slight duck-shaped gait. Peripheral blood DNA samples were collected from this child and her parents and brother to perform high-throughput whole-exome sequencing and high-throughput mitochondrial genome sequencing. Sanger sequencing was performed for verification. The results showed two compound heterozygous mutations, c.394C>T and c.447_449delGGAinsGT, in the C12orf65 gene. The former mutation came from her father and was a known pathogenic mutation, and the latter came from her mother and was a novel mutation which had not been reported in literature. This study expands the mutation spectrum of the C12orf65 gene and thus provides a molecular basis for the etiological diagnosis of the child and the genetic counseling of the family.
Child ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mitochondrial Proteins ; genetics ; Mutation ; Pedigree ; Peptide Termination Factors ; genetics ; Spastic Paraplegia, Hereditary ; genetics

Adult ; Female ; Humans ; Male ; Middle Aged ; Pedigree ; Spastic Paraplegia, Hereditary ; genetics

Exons ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Mutation ; Pedigree ; Spastic Paraplegia, Hereditary ; etiology ; genetics

Child ; Child, Preschool ; Humans ; Male ; Spastic Paraplegia, Hereditary ; genetics

Adult ; Family Health ; Female ; Humans ; Male ; Pedigree ; Spastic Paraplegia, Hereditary ; diagnosis ; genetics ; physiopathology