Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is a rare condition inherited as autosomal dominant trait and characterized by hypoparathyroidism, sensorineural deafness, and renal dysplasia. HDR syndrome is caused by haploinsufficiency of the GATA3 gene located on chromosome 10p15. Here, we report the case of a 32-day-old Korean male with HDR syndrome. He was presented due to repeated seizures over previous 3 days. The patient was born after 40 weeks of gestation with birth weight of 2930 g, and was the first-born baby of healthy Korean parents. Hypoparathyroidism was first noticed due to seizure. A multicystic left dysplastic kidney and vesicoureteral reflux were detected by ultrasound after birth. Auditory brainstem response (ABR) testing revealed that the patient had moderate sensorineural deafness, with hearing losses of 80 dB at the mid and higher frequencies for both ears. Echocardiography finding revealed secundum atrial septal deftect. Based on biochemical results and clinical findings, a presumptive diagnosis of HDR syndrome was made. GATA3 mutation analysis identified a heterozygous deletion, c.153del (p.Phe51Leufs*144) in exon 1 causing a frameshift mutation, which is a novel de novo mutation. Therefore, we suggest that HDR syndrome should be considered in the differential diagnosis in symptomatic or asymptomatic patients with hypoparathyroidism, and that renal ultrasound or ABR testing be performed to prevent a missed diagnosis. This is the first report on Korean patient with confirmed HDR syndrome with novel mutation.
Base Sequence ; DNA Mutational Analysis ; GATA3 Transcription Factor/genetics ; Hearing Loss, Sensorineural/*genetics/*pathology ; Heterozygote ; Humans ; Hypoparathyroidism/*genetics/*pathology ; Infant, Newborn ; Kidney/abnormalities/ultrasonography ; Male ; Molecular Sequence Data ; Nephrosis/*genetics/*pathology ; Reproducibility of Results ; Republic of Korea ; Sequence Deletion

Isolated hypoparathyroidism (IH) shows heterogeneous phenotypes and can be caused by defects in a variety of genes. The goal of our study was to determine the clinical features and to analyze gene mutations in a large cohort of Korean patients with sporadic or familial IH. We recruited 23 patients. They showed a broad range of onset age and various values of biochemical data. Whole exome sequencing was performed on two affected cases and one unaffected individual in a family. All coding exons and exon-intron borders of GCMB, CASR, and prepro-PTH were sequenced using PCR-amplified DNA. In one family who underwent the whole exome sequencing analysis, approximately 300 single nucleotide changes emerged as candidates for genetic alteration. Among them, we identified a functional mutation in exon 2 of GCMB (C106R) in two affected cases. Besides, heterozygous gain-of-function mutations in the CASR gene were found in other subjects; D410E and P221L. We also found one single nucleotide polymorphism (SNP) in the prepro-PTH gene, five SNPs in the CASR gene, and four SNPs in the GCMB gene. The current study represents a variety of biochemical phenotypes in IH patients with the molecular genetic diagnosis of IH.
Adult ; Aged ; Asian Continental Ancestry Group/*genetics ; Cohort Studies ; Heterozygote ; Humans ; Hypoparathyroidism/diagnosis/*genetics/pathology ; Middle Aged ; Nuclear Proteins/*genetics ; Parathyroid Hormone/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Receptors, Calcium-Sensing/*genetics ; Registries ; Republic of Korea ; Transcription Factors/*genetics ; Young Adult

Adenocarcinoma, Follicular ; radiotherapy ; secondary ; Adolescent ; Adult ; Aged ; Bone Neoplasms ; secondary ; Carcinoma, Papillary ; radiotherapy ; secondary ; Child ; Chromosome Aberrations ; radiation effects ; Dose-Response Relationship, Radiation ; Humans ; Hypoparathyroidism ; etiology ; Iodine Radioisotopes ; administration & dosage ; Lung ; physiopathology ; Lung Neoplasms ; secondary ; Lymphatic Metastasis ; Middle Aged ; Parathyroid Glands ; physiopathology ; Salivary Glands ; physiopathology ; Thyroid Neoplasms ; genetics ; pathology ; radiotherapy