A case of hypoparathyroidism, sensorineural deafness and renal disease (HDR) syndrome in a boy carrying a novel mutation of GATA3 gene

2020 ◽  
Author(s):  
Laura Mazoni ◽  
Matteo Apicella ◽  
Simona Borsari ◽  
Chiara Banti ◽  
Angela Michelucci ◽  
...  
Keyword(s):  
Renal Disease ◽  
Novel Mutation ◽  
Sensorineural Deafness ◽  
Hdr Syndrome

scholarly journals Unusual Proliferative Glomerulonephritis in a Patient Diagnosed to Have Hypoparathyroidism, Sensorineural Deafness, and Renal Dysplasia (HDR) Syndrome with a Novel Mutation in the GATA3 Gene

2017 ◽  
Vol 56 (11) ◽  
pp. 1393-1397 ◽  
Author(s):  
Michitsugu Kamezaki ◽  
Tetsuro Kusaba ◽  
Takaomi Adachi ◽  
Noriyuki Yamashita ◽  
Mayumi Nakata ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Sensorineural Deafness ◽  
Renal Dysplasia ◽  
Proliferative Glomerulonephritis ◽  
Hdr Syndrome ◽  
I Gene

scholarly journals HDR Syndrome (Hypoparathyroidism, Sensorineural Deafness and Renal Disease) Accompanied by Renal Tubular Acidosis and Endocrine Abnormalities

2008 ◽  
Vol 47 (11) ◽  
pp. 1003-1007 ◽  
Author(s):  
Abdullah Taslipinar ◽  
Levent Kebapcilar ◽  
Mustafa Kutlu ◽  
Mustafa Sahin ◽  
Aydogan Aydogdu ◽  
...  
Keyword(s):  
Renal Disease ◽  
Renal Tubular Acidosis ◽  
Sensorineural Deafness ◽  
Renal Tubular ◽  
Hdr Syndrome

scholarly journals Hypoparathyroidism, Sensorineural deafness and renal disease (Barakat syndrome) caused by a reduced gene dosage in GATA3: a case report and review of literature

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Anne D. D. Joseph ◽  
Nirmala D. Sirisena ◽  
Thirunavukarasu Kumanan ◽  
Vathualan Sujanitha ◽  
Veronika Strelow ◽  
...  
Keyword(s):  
Vitamin D ◽  
Hearing Loss ◽  
Renal Disease ◽  
Gene Deletion ◽  
Gene Dosage ◽  
Sensorineural Deafness ◽  
Renal Functions ◽  
Vitamin D Levels ◽  
25 Hydroxy Vitamin D ◽  
Hdr Syndrome

Abstract Background Barakat syndrome is an autosomal dominant rare genetic disease caused by haploinsufficiency of the GATA binding protein 3 (GATA3) gene. It is also known as HDR syndrome, and is characterized by varying degrees of hypoparathyroidism, sensorineural deafness and renal disease. This is the first report of a heterozygous GATA3 whole gene deletion causing HDR syndrome in a Sri Lankan family. Case presentation A 13-year-old boy with an acute febrile illness, hypocalcaemia and bilateral carpopedal spasm was referred for evaluation. A past medical history of treatment for persistent hypocalcaemic symptoms since the age of 7 months was obtained. Biochemical investigations showed persistent low serum corrected calcium levels with hyperphosphataemia, hypomagnesaemia, low parathyroid hormone levels, hypercalciuria, and low total 25-hydroxy vitamin D levels. His renal functions and renal sonography were normal. Audiometry showed bilateral moderate to severe sensorineural hearing loss. On screening, his mother was also found to have asymptomatic hypocalcaemia, hypomagnesaemia, hyperphosphataemia, hypercalciuria and low total 25-hydroxy vitamin D levels. She had impaired renal functions and chronic parenchymal changes in the renal scan. Audiometry showed bilateral profound sensorineural hearing loss. Genetic analysis using multiplex-ligation dependent probe amplification showed a reduced gene dosage for GATA3 that is consistent with a heterozygous whole gene deletion in both the child and mother. Conclusions This report demonstrates the wide intra-familial phenotypic variability observed in HDR syndrome and adds further to the existing scientific literature on the genotype-phenotype correlation of this syndrome. It highlights the need for HDR syndrome to be considered in the differential diagnosis of persistent hypocalcaemia with sensorineural deafness and/or renal involvement, and for appropriate genetic evaluation to be done to confirm the diagnosis.

A novel mutation in GATA3 gene in HDR syndrome

2014 ◽  
Author(s):  
Doo-Man Kim ◽  
Seung Yang ◽  
Juri Park ◽  
Ho Young Son
Keyword(s):  
Novel Mutation ◽  
Hdr Syndrome

scholarly journals HDR Syndrome Accompanying Type 1 Diabetes Mellitus and Hypopituitarism

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Mustafa Can ◽  
Feridun Karakurt ◽  
Muhammed Kocabas ◽  
İlker Cordan ◽  
Melia Karakose ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Autosomal Dominant ◽  
Sensorineural Deafness ◽  
Renal Dysplasia ◽  
Autosomal Dominant Disorder ◽  
Hdr Syndrome

HDR (Hypoparathyroidism, Deafness, and Renal Dysplasia) syndrome is an autosomal dominant disorder characterized by the triad of hypoparathyroidism, sensorineural deafness, and renal disease. Approximately 65% of patients with HDR syndrome have all three of these features, while others have different combinations of these features. We aimed to present a case with primary hypoparathyroidism, hearing loss, and nondiabetic chronic kidney disease and diagnosed as HDR syndrome while being followed up for type 1 diabetes mellitus and hypopituitarism.

scholarly journals SAT-065 A Novel De Novo GATA3 Gene Mutation in an Adolescent with HDR Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lisa Michelle Cruz-Aviles ◽  
Allen Bale ◽  
Thomas O Carpenter
Keyword(s):  
Hearing Aids ◽  
Slipped Capital Femoral Epiphysis ◽  
Family Members ◽  
Sensorineural Deafness ◽  
Incomplete Fusion ◽  
Heterozygous Mutation ◽  
Facial Dysmorphism ◽  
Intact Pth ◽  
Hdr Syndrome

Abstract Background: GATA3 encodes a transcription factor critical for embryonic development of the parathyroid glands, kidney, inner ear, thymus, and the central nervous system. Heterozygous loss-of-function mutations in GATA3 are associated with hypoparathyroidism, sensorineural deafness and renal disease (HDR syndrome). Clinical Case: A 12 yo male with left hip pain underwent a closed reduction for left slipped capital femoral epiphysis. The pre-op evaluation revealed hypocalcemia (serum Ca 7.7 mg/dL; nl: 8.8-10.2), creatinine 0.46 mg/dL (0.5-1.0), TSH 3.16 uU/mL (0.3-4.2), FT4 1.36 ng/dL (0.8-1.8). Oral calcium and vitamin D supplementation was begun, and 2 wks later, follow-up evaluation revealed serum Ca of 9.4 mg/dL, intact PTH 4.6 pg/mL (10-69), phosphorus 5.9 mg/dL (3.3-5.3), 25-OHD 26 ng/mL (30-100), and a normal chromosomal microarray. Bone density (DXA) Z-scores for hip and spine were -1.7 and 0.8, respectively. At age 13 he underwent bilateral osteotomy due to bilateral hip dysplasia and removal of hardware the next year. At age 15 he underwent left total hip replacement for avascular necrosis. In the post-operative period hypocalcemia recurred (5.9-6.7mg/dL), and he was referred for endocrine evaluation. He was of mixed African American and Puerto-Rican descent. He had difficulties in school and required eyeglasses and hearing aids. Past history included congenital scoliosis (right T11-12 rib fusion, wedged L1 vertebra, and incomplete fusion of posterior elements of L4 and L5), a small right kidney (per ultrasound examination), bilateral orchiopexy for undescended testicles (age 2), diagnoses of ADHD (at age 5); sensorineural hearing loss and psoriasis (age 12), and gastroesophageal reflux (age13). Multiple paternal family members were reported to have abnormal calcium levels and hearing/vision problems, but no known diagnosis. On exam, he had no facial dysmorphism, but left supernumerary nipples, lumbar lordosis and thoracic kyphosis, and clinodactyly. He had achieved Tanner 5 secondary sexual characteristics. There was no Chvostek’s sign. Laboratory investigation revealed Ca 7.9 mg/dL, phosphorus 5.9 mg/dL (3.1-4.7), alkaline phosphatase 123 U/L (50-380), 25-OHD 32 ng/mL, intact PTH 10.2 pg/mL. Treatment with calcium carbonate and calcitriol was begun. Whole exome sequencing identified a heterozygous mutation in GATA3 (c.1061C>T, p.Pro354Leu), predicted to be damaging. This variant has not been reported in literature or public database to our knowledge. Conclusion: This case highlights the importance of genetic testing in the setting of unexplained hypoparathyroidism, and identifies a likely novel mutation in GATA3, providing a basis to counsel the family and encourage medical follow up of suspected family members. References: Barakat, A., et al., Familial nephrosis, nerve deafness, and hypoparathyroidism. J Pediatr 91:61-64, 1977

scholarly journals Autosomal recessive Alport syndrome: mutation in the COL4A3 gene in a woman with Alport syndrome and posttransplant antiglomerular basement membrane nephritis.

1995 ◽  
Vol 5 (9) ◽  
pp. 1714-1717
Author(s):  
J Ding ◽  
J Stitzel ◽  
P Berry ◽  
E Hawkins ◽  
C E Kashtan
Keyword(s):  
Basement Membrane ◽  
Renal Disease ◽  
Alport Syndrome ◽  
Autosomal Recessive ◽  
Type Iv Collagen ◽  
Premature Stop Codon ◽  
Sensorineural Deafness ◽  
Type Iv ◽  
Base Pair Deletion ◽  
Carboxy Terminal

Autosomal recessive Alport syndrome can arise from a mutation in either of the genes COL4A3 and COL4A4 on chromosome 2, which encode, respectively, the alpha 3 and alpha 4 chains of Type IV collagen. This report describes a mutation in COL4A3 in a girl who presented at age 5 with hematuria and proteinuria, lacking any family history of renal disease. Renal biopsy at age 8 showed immunoglobulin A nephropathy and Alport syndrome. Sensorineural deafness developed during adolescence, and the patient's renal disease progressed to terminal renal failure by age 20. She received a living related donor renal allograft at age 20 and developed antiglomerular basement membrane nephritis of the allograft 8 months after transplantation. Amplification and sequencing of exon 5 of COL4A3 (counting from the 3' end of the gene) revealed a 7-base-pair deletion, producing a shift of the reading frame and the creation of a premature stop codon. Each parent was heterozygous for the normal and mutant exon 5 sequences. This mutation in COL4A3 would result in the loss of 222 amino acids from the carboxy-terminal noncollagenous domain of the alpha 3(IV) chain. The mutant chain would be unable to form trimers with other Type IV collagen alpha chains. In addition, the mutant chain would lack the Goodpasture epitope, which resides in the carboxy-terminal noncollagenous domain of the alpha 3(IV) chain. The absence of this epitope may underly the subsequent development of anti-glomerular basement membrane nephritis in the allograft.

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