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 "mental retardation" symptom

achondroplasia

alexander disease

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

classical phenylketonuria

coats disease

cohen syndrome

cowden syndrome

cystinuria

dentin dysplasia

familial hypocalciuric hypercalcemia

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

kabuki syndrome

kallmann syndrome

lamellar ichthyosis

lymphangioleiomyomatosis

monosomy 21

phenylketonuria

primary hyperoxaluria type 1

proteus syndrome

pyruvate dehydrogenase deficiency

sneddon syndrome

triple a syndrome

wolf-hirschhorn syndrome

zellweger syndrome

This symptom has already been validated