OBJECTIVE: To explore the genetic basis for a child with succinate semialdehyde dehydrogenase deficiency. METHODS: Peripheral blood samples of the proband and his parents were collected and subjected to Sanger sequencing. High-throughput sequencing was used to verify the gene variants. Bioinformatic software was used to analyze the pathogenicity of the variant sites. RESULTS: Sanger sequencing showed that the proband carried a homozygous c.1529C>T (p.S510F) variant of the ALDH5A1 gene, for which his mother was a carrier. The same variant was not detected in his father. However, high-throughput sequencing revealed that the child and his father both had a deletion of ALDH5A1 gene fragment (chr6: 24 403 265-24 566 986). CONCLUSION The c.1529C>T variant of the ALDH5A1 gene and deletion of ALDH5A1 gene fragment probably underlay the disease in the child. High-throughput sequencing can detect site variation as well as deletion of gene fragment, which has enabled genetic diagnosis and counseling for the family.
Amino Acid Metabolism, Inborn Errors/genetics* ; Child ; Developmental Disabilities ; Humans ; Infant ; Mutation ; Succinate-Semialdehyde Dehydrogenase/genetics*

OBJECTIVETo detect potential mutation in a Chinese family affected with succinic semialdehyde dehydrogenase deficiency.

METHODSGenomic DNA was extracted from the peripheral blood samples of the proband, her family members and 100 healthy controls. All exons and flanking intronic regions of the ALDH5A1 gene were amplified by PCR and subjected to direct sequencing.

RESULTSThe proband was found to have compound heterozygous mutations of the ALDH5A1 gene, namely c.398_399delAA (p.N134X) and c.638G>T (p.R213L), for which her parents were both heterozygous carriers. The same mutations were not found among the 100 healthy controls.

CONCLUSIONThe novel mutations of the ALDH5A1 gene probably underlie the pathogenesis of the disease in the infant, which also enriched the mutation spectrum of the ALDH5A1 gene.

Amino Acid Metabolism, Inborn Errors ; ethnology ; genetics ; Amino Acid Sequence ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; China ; DNA Mutational Analysis ; methods ; Developmental Disabilities ; ethnology ; genetics ; Exons ; genetics ; Family Health ; Female ; Heterozygote ; Humans ; Infant ; Introns ; genetics ; Male ; Mutation ; Sequence Homology, Amino Acid ; Succinate-Semialdehyde Dehydrogenase ; deficiency ; genetics

OBJECTIVETo detect potential mutation in ALDH5A1 gene for a family affected with succinic semialdehyde dehydrogenase deficiency diagnosed by clinical inspection and urine screening.

METHODSPolymerase chain reaction and direct DNA sequencing were carried out for the affected child and her parents. Suspected ALDH5A1 gene mutations were verified in 100 healthy controls to exclude polymorphisms.

RESULTSThe child was found to have carried 2 heterozygous missense mutations in the coding region of ALDH5A1 gene, namely c.527G>A and c.691G>A, for which her mother and father were respectively heterozygotes. The same mutations were not detected in 100 healthy controls. The child was also found to have carried two previously described polymorphisms including a heterozygous c.545C>T(derived from her father) and a homozygous c.538C>T(derived from her mother).

CONCLUSIONMissense mutations of c.527G>A and c.691G>A in the ALDH5A1 gene are responsible for the pathogenesis of the disease in this family.

Adult ; Amino Acid Metabolism, Inborn Errors ; enzymology ; ethnology ; genetics ; Amino Acid Sequence ; Animals ; Asian Continental Ancestry Group ; ethnology ; genetics ; Base Sequence ; Child, Preschool ; China ; ethnology ; Developmental Disabilities ; Female ; Heterozygote ; Humans ; Male ; Molecular Sequence Data ; Mutation, Missense ; Pedigree ; Polymorphism, Genetic ; Succinate-Semialdehyde Dehydrogenase ; deficiency ; genetics