title: Recurrent truncating mutations in alanine-glyoxylate aminotransferase gene in two South Indian families with primary hyperoxaluria type 1 causing later onset end-stage kidney disease.
abstract: Primary hyperoxaluria type 1 is an autosomal recessive inborn error of metabolism due to liver-specific peroxisomal enzyme alanine-glyoxylate transaminase deficiency. Here, we describe two unrelated patients who were diagnosed to have primary hyperoxaluria. Homozygous c.445_452delGTGCTGCT (p.L151Nfs*14) (Transcript ID: ENST00000307503; human genome assembly GRCh38.p2) (HGMD ID CD073567) mutation was detected in both the patients and the parents were found to be heterozygous carriers. Our patients developed end-stage renal disease at 23 years and 35 years of age. However, in the largest series published from OxalEurope cohort, the median age of end-stage renal disease for null mutations carriers was 9.9 years, which is much earlier than our cases. Our patients had slower progressions as compared to three unrelated patients from North India and Pakistan, who had homozygous c.302T>C (p.L101P) (HGMD ID CM093792) mutation in exon 2. Further, patients need to be studied to find out if c.445_452delGTGCTGCT mutation represents a founder mutation in Southern India.
authors: Department of Medical Genetics, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.
authors: A K
authors: AK
authors: Dutta
authors: Department of Nephrology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.
authors: B K
authors: BK
authors: Paulose
authors: Department of Medical Genetics, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.
authors: S
authors: S
authors: Danda
authors: Department of Nephrology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.
authors: S
authors: S
authors: Alexander
authors: Department of Nephrology, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.
authors: V
authors: V
authors: Tamilarasi
authors: Department of Medical Genetics, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.
authors: S
authors: S
authors: Omprakash
keywords: Alanine-glyoxylate transaminase; India; chronic; nephrolithiasis; primary hyperoxaluria type 1; renal insufficiency