1. HDR syndrome: A novel 'de novo' mutation in GATA3 gene
- Author
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S. Ferraris, Roberto Lala, Alberto Ponzone, Angelo Giovanni Del monaco, Patrizia Pappi, Emanuela Garelli, Barbara De Vito, and Adriana Carando
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Adolescent ,Hypoparathyroidism ,HDR syndrome ,Hearing Loss, Sensorineural ,DNA Mutational Analysis ,Molecular Sequence Data ,Bilateral Deafness ,GATA3 Transcription Factor ,Kidney ,Nystagmus, Pathologic ,Frameshift mutation ,Exon ,deafness ,Internal medicine ,Genetics ,medicine ,Blepharoptosis ,Humans ,Amino Acid Sequence ,Frameshift Mutation ,Genetics (clinical) ,Sequence Deletion ,Base Sequence ,business.industry ,Unilateral renal dysplasia ,hypoparathyroidism ,renal anomalies ,GATA3 gene ,GATA3 ,DNA ,Syndrome ,Renal dysplasia ,Endocrinology ,Palpebral fissure ,Codon, Nonsense ,Mutation ,business ,Haploinsufficiency - 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. © 2009 Wiley-Liss, Inc.
- Published
- 2009