Common mutation underlying primary hyperoxaluria type1 in three Indian children

Chanchlani, Rahul; Sinha, Aditi; Gulati, Ashima; Agarwal, Vikas; Bagga, Arvind

doi:10.4103/0971-4065.106044

Cited by 11 publications

(14 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[8] The PH 2 mutations c. 103delG and c. 403_404+2delAAGT are the most common; the latter predominates in Asians. [4] However, the different set of mutations detected in our patients substantiates that these previously reported mutational hot spots may be population specific.…”

Section: Discussionmentioning

confidence: 99%

Clinical and genetic profile of Indian children with primary hyperoxaluria

et al. 2017

View full text Add to dashboard Cite

Primary hyperoxaluria (PH) has heterogeneous renal manifestations in infants and children. This often leads to delay in diagnosis. In the past 3 years, genetic samples were sent for seven children with a clinical diagnosis of PH. Their medical records were reviewed for clinical presentation and outcomes. Of the seven children, three were males. The median age of presentation was 4.9 years with the youngest presenting at 3 months of age. Nephrolithiasis, the most common presentation was associated with renal dysfunction in two children. Two children with no significant history presented in end-stage renal disease (ESRD). The sibling of one of the children in ESRD, with a history of consanguinity in parents, was screened for asymptomatic nephrolithiasis. Bilateral multiple renal calculi were found in majority of children followed by echogenic kidneys on ultrasound examination. Genetic analysis suggested PH Type 1 in five children and type 2 in two children. The mutations detected in our cohort were different from the previously reported common mutations. There was no obvious genotype-phenotype correlation noticed. Three children in ESRD are on maintenance dialysis. Nephrolithiasis being a common presentation of PH needs prompt evaluation. Mutations are generally population specific, and whole gene sequence analysis is critical in diagnosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Clinical and genetic profile of Indian children with primary hyperoxaluria

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Although the occurrence of nephrocalcinosis and nephrolithiasis is known in Indian children,[ 10 ] screening for hyperoxaluria is rarely performed. [ 11 ] The diagnosis of PH Type 1 is suspected in any child with an elevated urinary oxalate excretion (>0.5 mmol [45 mg]/1.73 m 2 /day). [ 1 ] PH Type 1 can be confirmed by identification of biallelic pathogenic variants in the AGXT gene.…”

Section: Discussionmentioning

confidence: 99%

“…Chanchlani et al . [ 11 ] and Sethi et al . [ 18 ] described North Indian children affected by PH Type 1 who were homozygous for the c. 302T>C (p. Leu101Pro) AGXT mutation.…”

Section: Discussionmentioning

confidence: 99%

“…It is also pertinent to note that these two mutations encountered in our patient, although reported in the AGXT mutation database,[ 13 ] are different from those reported in other Indian children or adults. [ 11 18 19 ] Considering the scanty literature regarding mutational analysis in childhood-onset PH Type 1 from India, in general, and South India, in particular,[ 19 ] this work has the merit to expand the spectrum of genotypes encountered in Indian PH Type 1 patients.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Primary hyperoxaluria Type 1 with homozygosity for a double-mutated AGXT allele in a 2-year-old child

et al. 2017

View full text Add to dashboard Cite

Primary hyperoxaluria (PH) Type 1 is a rare, genetic disorder caused by deficiency of the liver enzyme alanine-glyoxylate aminotransferase, which is encoded by AGXT gene. We report a 2-year-old South Indian Tamil child with nephrocalcinosis due to PH Type 1, in whom a homozygous genotype for two missense mutations in the AGXT gene was found: first, a C to G transversion (c. 32C>G) in exon 1 resulting in the amino acid substitution p.Pro11Arg; second, a T to A transversion (c. 167T>A) in exon 2 resulting in p.Ile56Asn. A therapy based on potassium citrate and pyridoxine was started. This is the first report of molecular testing-proven childhood onset-PH Type 1 from South India and is notable for the co-occurrence of two missense mutations in one AGXT allele, which might lead to different and more severe phenotype than each mutation alone. To the best of our knowledge, AGXT allele carrying two already known mutations has not been previously reported.

show abstract

“…Primary hyperoxaluria type 1 (PH1) (OMIM 259900) is an autosomal recessive inborn error of metabolism due to deficiency of liver-specific peroxisomal enzyme alanine-glyoxylate transaminase (AGT). Until date, only three genetically confirmed cases have been reported from North India[ 1 ] (tests undertaken in The Netherlands) and none from South India. Here, we report two unrelated patients from South India having recurrent mutations in exon 4 of alanine-glyoxylate aminotransferase (AGXT) gene (tests done in our institution).…”

Section: Introductionmentioning

confidence: 99%

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

Dutta¹,

Paulose²,

Danda³

et al. 2016

Indian J Nephrol

View full text Add to dashboard Cite

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.

show abstract

Common mutation underlying primary hyperoxaluria type1 in three Indian children

Cited by 11 publications

References 11 publications

Clinical and genetic profile of Indian children with primary hyperoxaluria

Clinical and genetic profile of Indian children with primary hyperoxaluria

Primary hyperoxaluria Type 1 with homozygosity for a double-mutated AGXT allele in a 2-year-old child

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

Contact Info

Product

Resources

About