Identification of a novel de novo GATA3 mutation in a patient with HDR syndrome
Liu Chen1, Bing Chen1, Wuilin Leng1
1Department of Endocrinology, First Affiliated Hospital of Third Military Medical University, Chongqing, China.
Insights
This study presents a case of hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome in a young male. A novel GATA3 gene mutation was identified, reinforcing its role in HDR syndrome pathogenesis.
Area of Science:
- Genetics
- Nephrology
- Endocrinology
Background:
- Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare genetic disorder.
- Genetic mutations, particularly in the GATA3 gene, are implicated in HDR syndrome.
Observation:
- A 21-year-old male presented with hypocalcemia, hyperphosphatemia, limb twitching, deafness, proteinuria, elevated creatinine and urea, and kidney shrinkage.
- Brain CT revealed intracranial calcifications.
Findings:
- The patient was diagnosed with HDR syndrome.
- DNA analysis identified a novel de novo frameshift mutation (c. 529dupC) in the GATA3 gene.
- This mutation leads to a premature stop codon, suggesting GATA3 haploinsufficiency.
Implications:
- This case provides further evidence linking GATA3 gene mutations to HDR syndrome.
- Understanding the genetic basis of HDR syndrome aids in diagnosis and potential therapeutic strategies.
- Highlights the importance of genetic testing in patients with complex syndromic presentations.
Abstract:
We describe the case of a 21-year-old male with hypocalcaemia, hyperphosphataemia, recurrent limb twitch, deafness, proteinuria, increased serum creatinine and urea nitrogen levels, and shrinkage of both kidneys. Brain computed tomography showed intracranial calcifications. The patient was diagnosed with hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) syndrome. DNA sequence analysis of the GATA3 gene showed a novel de novo mutation, c. 529dupC (p. Arg177profs*126), in exon 2, resulting in a frameshift mutation with a premature stop codon after a new 126 amino acid sequence. We provide further evidence that HDR syndrome is caused by haploinsufficiency of GATA3.
