RGD Reference Report - A Novel TBX1 Variant Causing Hypoparathyroidism and Deafness. - Rat Genome Database

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A Novel TBX1 Variant Causing Hypoparathyroidism and Deafness.

Authors: Alghamdi, Malak  Al Khalifah, Reem  Al Homyani, Doua K  Alkhamis, Waleed H  Arold, Stefan T  Ekhzaimy, Aishah  El-Wetidy, Mohammed  Kashour, Tarek  Halwani, Rabih 
Citation: Alghamdi M, etal., J Endocr Soc. 2019 Nov 29;4(2):bvz028. doi: 10.1210/jendso/bvz028. eCollection 2020 Feb 1.
RGD ID: 155641234
Pubmed: PMID:32110744   (View Abstract at PubMed)
PMCID: PMC7041699   (View Article at PubMed Central)
DOI: DOI:10.1210/jendso/bvz028   (Journal Full-text)


BACKGROUND: The TBX1 gene encodes the T-box 1 protein that is a transcription factor involved in development. Haploinsufficiency of the TBX1 gene is reported to cause features similar to DiGeorge syndrome. The TBX1 gene is located within the DiGeorge syndrome region, and studies support that the TBX1gene is responsible for most of the features of the phenotype of hemizygous deletion of chromosome 22q11.2. In this study, we report a family of 4 (a father with 3 children) who presented with congenital hypoparathyroidism and hypocalcemia, facial asymmetry, deafness, normal intelligence, and no cardiac involvement.
METHODS: We performed whole genome sequencing, computational structural analysis of the mutants, and gene expression studies for all affected family members.
RESULTS: Whole genome sequencing revealed a paternal inherited novel heterozygous variant, c.1158_1159delinsT p.(Gly387Alafs*73), in the exon 9 isoform C TBX1 gene, causing a loss of nuclear localization sequence (NLS) and transactivation domain (TAD) with no change in gene expression and resulted in a DiGeorge-like phenotype.
CONCLUSION: A pathogenic variant in the TBX1 gene exon 9 C that predicted to cause a loss in the NLS region and most of TAD leads to variable features of hypoparathyroidism, distinctive facial features, deafness, and no cardiac involvement. In addition, our report and previous reports indicate the presence of a wide phenotypic spectrum of TBX1 genetic variants and the consistent absence of cardiac involvement in the case of pathogenic variants on exon 9 isoform C TBX1 gene.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TBX1Humanepilepsy  IAGP DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
Tbx1Ratepilepsy  ISOTBX1 (Homo sapiens)DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
Tbx1Mouseepilepsy  ISOTBX1 (Homo sapiens)DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
TBX1HumanHypocalcemia  IAGP DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
Tbx1RatHypocalcemia  ISOTBX1 (Homo sapiens)DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
Tbx1MouseHypocalcemia  ISOTBX1 (Homo sapiens)DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
TBX1Humanhypoparathyroidism  IAGP DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
Tbx1Rathypoparathyroidism  ISOTBX1 (Homo sapiens)DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
Tbx1Mousehypoparathyroidism  ISOTBX1 (Homo sapiens)DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
TBX1Humansensorineural hearing loss  IAGP DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
Tbx1Ratsensorineural hearing loss  ISOTBX1 (Homo sapiens)DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 
Tbx1Mousesensorineural hearing loss  ISOTBX1 (Homo sapiens)DNA:frameshift mutation:CDS:p.G387AfsX73 (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TBX1HumanBilateral sensorineural hearing impairment  IAGP DNA:frameshift mutation:CDS:p.G387AfsX73RGD 
TBX1HumanHypocalcemia  IAGP DNA:frameshift mutation:CDS:p.G387AfsX73RGD 
TBX1HumanHypoparathyroidism  IAGP DNA:frameshift mutation:CDS:p.G387AfsX73RGD 
TBX1HumanSeizure  IAGP DNA:frameshift mutation:CDS:p.G387AfsX73RGD 
Objects Annotated

Genes (Rattus norvegicus)
Tbx1  (T-box transcription factor 1)

Genes (Mus musculus)
Tbx1  (T-box 1)

Genes (Homo sapiens)
TBX1  (T-box transcription factor 1)


Additional Information