title: Primary hyperoxaluria type 1 and brachydactyly mental retardation syndrome caused by a novel mutation in AGXT and a terminal deletion of chromosome 2.
abstract: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive disorder caused by mutations in the alanine:glyoxylate aminotransferase (AGXT) gene, located on chromosome 2q37. Mutant AGXT leads to excess production and excretion of oxalate, resulting in accumulation of calcium oxalate in the kidney, and progressive loss of renal function. Brachydactyly mental retardation syndrome (BDMR) is an autosomal dominant disorder, caused by haploinsufficiency of histone deacetylase 4 (HDAC4), also on chromosome 2q37. It is characterized by skeletal abnormalities and developmental delay. Here, we report on a girl who had phenotypes of both PH1 and BDMR. PCR-sequencing of the coding regions of AGXT showed a novel missense mutation, c.32C>G (p.Pro11Arg) inherited from her mother. Functional analyses demonstrated that it reduced the enzymatic activity to 31% of the wild-type and redirected some percentage of the enzyme away from the peroxisome. Microsatellite and array-CGH analyses indicated that the proband had a paternal de novo telomeric deletion of chromosome 2q, which included HDAC4. To our knowledge, this is the first report of PH1 and BDMR, with a novel AGXT mutation and a de novo telomeric deletion of chromosome 2q.
authors: Faculty of Science, Human Genetics Research, Department of Botany, Chulalongkorn University, Bangkok, Thailand.
authors: Rachaneekorn
authors: R
authors: Tammachote
authors: Nelawat
authors: N
authors: Kingsuwannapong
authors: Siraprapa
authors: S
authors: Tongkobpetch
authors: Chalurmpon
authors: C
authors: Srichomthong
authors: Patra
authors: P
authors: Yeetong
authors: Pornchai
authors: P
authors: Kingwatanakul
authors: Carla G
authors: CG
authors: Monico
authors: Kanya
authors: K
authors: Suphapeetiporn
authors: Vorasuk
authors: V
authors: Shotelersuk
mesh_terms: D059327:Brachydactyly / Q000235:genetics*; D002675:Child, Preschool; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2; D005260:Female; D006239:Haplotypes; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000235:genetics*; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008856:Microscopy, Fluorescence; D009154:Mutation; D010375:Pedigree; D013347:Subcellular Fractions / Q000201:enzymology; D000637:Transaminases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000637:Transaminases; C019635:Alanine-glyoxylate transaminase