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

Wang, Li; Lin, Qiongfen; Wang, Hongyang; Guan, Jing; Lan, Lan; Xie, Linyi; Yu, Lan; Yang, Ju Dong; Zhao, Cui; Liang, Jinlong; Zhou, Hanlin; Yang, Huanming; Xiong, Wenping; Zhang, Qiu-Jing; Wang, Dayong; Wang, Qiuju

doi:10.4103/0366-6999.201600

Cited by 5 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GATA3 testing revealed abnormalities in some of these patients but not in others (Chen et al, ; Lichtner et al, ). Patients from one family with autosomal dominant “D” were found to have the HDR syndrome by genetic testing although there were no signs or symptoms of “H” or “R” (Wang et al, ). The three hearing‐impaired family members in this report carried the same GATA3 mutation.…”

Section: Definition Of the Syndromementioning

confidence: 99%

“…The three hearing‐impaired family members in this report carried the same GATA3 mutation. The heterozygous c.826C > T (NM 002051.2), a nonsense mutation located within exon 4 that resulted in a premature termination codon (R276) in these patients was predicted to lead to GATA3 haploinsufficiency (Wang et al, ). The normal member among the siblings did not have the mutation.…”

Section: Definition Of the Syndromementioning

confidence: 99%

See 1 more Smart Citation

Barakat syndrome revisited

Barakat

Raygada

Rennert

2018

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Barakat syndrome also known as HDR syndrome (Online Mendelian Inheritance in Man [OMIM] 146255), was first described by Barakat et al. in . It is a rare genetic disorder characterized by the triad of hypoparathyroidism "H," sensorineural deafness "D," and renal disease "R." The defect is caused by deletions in chromosome 10p14 or mutations in the GATA3 gene. Although the syndrome has been phenotypically defined by this triad the literature identifies cases with different components with, or without GATA3 defects making the definition of the syndrome confusing. We analyzed 180 cases and attempted to define the phenotype of the syndrome and suggest guidelines for diagnosis. We suggest that the diagnosis could be confirmed in patients who have all three components, and in those who have two components with a positive family history. GATA3 testing is optional to establish the diagnosis in these patients. The syndrome should be considered in patients with isolated "D" where other causes of "D" have been excluded and those with isolated "R," especially if there is family history of any of these components. In these instances, confirmatory GATA3 testing is indicated to confirm the diagnosis. In patients with nonsurgical "H," where "D" and "R" have been conclusively ruled out GATA3 studies are not needed as none of these patients were shown to be GATA3 haploinsufficient. Only 64.4% of patients in our review had "HDR." Some findings might have not been recognized or may could have appeared later in life, but it is evident that this syndrome is genotypically heterogeneous.

show abstract

Section: Definition Of the Syndromementioning

confidence: 99%

Section: Definition Of the Syndromementioning

confidence: 99%

Barakat syndrome revisited

Barakat

Raygada

Rennert

2018

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…It has been suggested that in some families with HDR, there is a mechanism of genetic anticipation, by which each generation exhibits an earlier onset or greater severity of the disease, than the previous generation (L. Wang et al, 2017). However, this may also be explained by ascertainment bias, as prior knowledge of the family history of an abnormality is more likely to lead to greater awareness of the disorder and to earlier screening and diagnosis of abnormalities in the next generation.…”

Section: Discussionmentioning

confidence: 99%

“…GATA3 mutations are usually identified in patients with two or three of the HDR triad features (Ali et al, 2007) with previously unrecognized HDR syndrome (Cabanillas et al, 2018). Other studies of families with apparently isolated autosomal dominant hearing loss, using NGS panels, revealed that the cause of the deafness was GATA3 mutations and that other previously undetected HDR features were also present (Lin et al, 2015;L. Wang et al, 2017 Wang et al, 2019).…”

Section: Diagnostic Relevancementioning

confidence: 99%

“…The primary hypoparathyroidism is characterized by symptomatic or asymptomatic hypocalcaemia with undetectable or inappropriately normal serum concentrations of parathyroid hormone (PTH) (Thakker, 2011). The deafness is sensorineural and is usually bilateral and more pronounced at higher frequencies (van Looij et al, 2006;L. Wang et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hypoparathyroidism, deafness, and renal dysplasia syndrome: 20 Years after the identification of the firstGATA3mutations

Lemos

Thakker

2020

Human Mutation

View full text Add to dashboard Cite

The hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by heterozygous mutations of the GATA3 gene. In the last 20 years, since the identification of the genetic cause of the HDR syndrome, GATA3 mutations have been reported in 124 families (177 patients). The clinical aspects and molecular genetics of the HDR syndrome are reviewed here together with the reported mutations and phenotypes. Reported mutations consist of 40% frameshift deletions or insertions, 23% missense mutations, 14% nonsense mutations, 6% splice‐site mutations, 1% in‐frame deletions or insertions, 15% whole‐gene deletions, and 1% whole‐gene duplication. Missense mutations were found to cluster in the regions encoding the two GATA3 zinc‐finger domains. Patients showed great clinical variability and the penetrance of each HDR defect increased with age. The most frequently observed abnormality was deafness (93%), followed by hypoparathyroidism (87%) and renal defects (61%). The mean age of diagnosis of HDR was 15.3, 7.5, and 14.0 years, respectively. However, patients with whole‐gene deletions and protein‐truncating mutations were diagnosed earlier than patients with missense mutations.

show abstract