Dataset Information

Clinical Auditory Phenotypes Associated with GATA3 Gene Mutations in Familial Hypoparathyroidism-deafness-renal Dysplasia Syndrome.

ABSTRACT: Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases.Three affected family members underwent otologic examinations, biochemistry tests, and other clinical evaluations. Targeted genes capture combining next-generation sequencing was performed within the family. Sanger sequencing was used to confirm the causative mutation. The auditory phenotypes of all reported familial HDR syndrome cases analyzed were provided.In Chinese family 7121, a heterozygous nonsense mutation c.826C>T (p.R276*) was identified in GATA3. All the three affected members suffered from sensorineural deafness and hypocalcemia; however, renal dysplasia only appeared in the youngest patient. Furthermore, an overview of thirty HDR syndrome families with corresponding GATA3 mutations revealed that hearing impairment occurred earlier in the younger generation in at least nine familial cases (30%) and two thirds of them were found to carry premature stop mutations.This study highlights the phenotypic heterogeneity of HDR and points to a possible genetic anticipation in patients with HDR, which needs to be further investigated.

SUBMITTER: Wang L

PROVIDER: S-EPMC5358421 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

Clinical Auditory Phenotypes Associated with <i>GATA3</i> Gene Mutations in Familial Hypoparathyroidism-deafness-renal Dysplasia Syndrome.

Wang Li L Lin Qiong-Fen QF Wang Hong-Yang HY Guan Jing J Lan Lan L Xie Lin-Yi LY Yu Lan L Yang Ju J Zhao Cui C Liang Jin-Long JL Zhou Han-Lin HL Yang Huan-Ming HM Xiong Wen-Ping WP Zhang Qiu-Jing QJ Wang Da-Yong DY Wang Qiu-Ju QJ

Chinese medical journal 20170301 6

<h4>Background</h4>Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases.<h4>Methods</h4>Three affected family members underwent ...[more]

PMID: 28303854

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Project description: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.

Dataset Information

Clinical Auditory Phenotypes Associated with GATA3 Gene Mutations in Familial Hypoparathyroidism-deafness-renal Dysplasia Syndrome.

Publications

Clinical Auditory Phenotypes Associated with <i>GATA3</i> Gene Mutations in Familial Hypoparathyroidism-deafness-renal Dysplasia Syndrome.

Similar Datasets

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