Primary hyperoxaluria type 1 and brachydactyly mental retardation syndrome caused by a novel mutation in AGXT and a terminal deletion of chromosome 2.

[primary hyperoxaluria type 1]

Primary hyperoxaluria type 1 (PH 1 ) is an autosomal recessive disorder caused by mutations in the alanine :glyoxylate aminotransferase (AGXT ) gene , located on chromosome 2 q 37 . 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 (HDAC 4 ), also on chromosome 2 q 37 . It is characterized by skeletal abnormalities and developmental delay . Here , we report on a girl who had phenotypes of both PH 1 and BDMR . PCR-sequencing of the coding regions of AGXT showed a novel missense mutation , c .32 C >G (p .Pro 11 Arg ) 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 2 q , which included HDAC 4 . To our knowledge , this is the first report of PH 1 and BDMR , with a novel AGXT mutation and a de novo telomeric deletion of chromosome 2 q .

Diseases
Validation

Diseases presenting "hyperoxaluria" symptom

cystinuria

neonatal adrenoleukodystrophy

primary hyperoxaluria type 1

This symptom has already been validated