title: HDR syndrome: a novel "de novo" mutation in GATA3 gene.
abstract: Human GATA3 haploinsufficiency leads to HDR (hypoparathyroidism, deafness, and renal dysplasia) syndrome. The development of a specific subset of organs in which this transcription factor is expressed appears exquisitely sensitive to gene dosage. We report on a 14-year-old patient with symptomatic hypoparathyroidism, sensorineural bilateral deafness, unilateral renal dysplasia, bilateral palpebral ptosis, and horizontal nystagmus. Fundoscopy displayed symmetrical pseudopapilledema, and brain CT scan revealed basal ganglia calcifications. FISH analysis did not disclose any microdeletion in the 22q11.2 or 10p14 regions. GATA3 mutation analysis identified a heterozygous deletion of GG nucleotides at codon 36 and 37 (c.108_109delGG) in exon 2 causing a frameshift with a premature stop codon after a new 15-aminoacid sequence. Restriction endonuclease analysis performed in parents was negative. Our patient carries a novel "de novo" GATA3 mutation, providing further evidence that HDR syndrome is caused by haploinsufficiency of GATA3, which may be responsible for a complex neurologic picture besides the known triad.
authors.affiliation: Department of Pediatrics, University of Torino, Torino, Italy. silvio.ferraris@unito.it
authors.forename: Silvio
authors.initials: S
authors.lastname: Ferraris
authors.forename: Angelo Giovanni
authors.initials: AG
authors.lastname: Del Monaco
authors.forename: Emanuela
authors.initials: E
authors.lastname: Garelli
authors.forename: Adriana
authors.initials: A
authors.lastname: Carando
authors.forename: Barbara
authors.initials: B
authors.lastname: De Vito
authors.forename: Patrizia
authors.initials: P
authors.lastname: Pappi
authors.forename: Roberto
authors.initials: R
authors.lastname: Lala
authors.forename: Alberto
authors.initials: A
authors.lastname: Ponzone
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001483:Base Sequence; D001763:Blepharoptosis / Q000235:genetics; D018389:Codon, Nonsense; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D016368:Frameshift Mutation; D050990:GATA3 Transcription Factor / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007011:Hypoparathyroidism / Q000235:genetics*; D007668:Kidney / Q000002:abnormalities*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009759:Nystagmus, Pathologic / Q000235:genetics; D017384:Sequence Deletion; D013577:Syndrome
chemical_list: D018389:Codon, Nonsense; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D004247:DNA