Novel homozygous mutation in SCNN1A gene in an Iranian boy with PHA1B.

OBJECTIVES: Pseudohypoaldosteronism type 1 (PHA1) has two genetically distinct variants, including renal and systemic forms. Systemic PHA type I (PHA1B) has varying degrees of clinical presentation and results from mutations in genes encoding subunits of the epithelial sodium channel (ENaC) including the alpha, beta, and gamma subunits. To date, about 45 variants of PHA1B have been identified. CASE PRESENTATION: We report a boy with PHA1B, who presented with vomiting, lethargy, and poor feeding due to salt wasting six days after birth. The patient had electrolyte imbalances. A novel SCNN1A (sodium channel epithelial subunit alpha) gene mutation, NM_001038.6:c.1497G>C, with an autosomal recessive pattern, was identified by whole exosome sequencing. This variant was inherited as a homozygote from both heterozygous parents. CONCLUSIONS: PHA should be considered in neonates with hyponatremia and hyperkalemia. This case report presents a patient with a novel mutation in SCNN1A that has not been previously reported. Long-term follow-up of identified patients to understand the underlying phenotype--genotype link is necessary.

Novel Homozygous Nonsense Mutation in the LRP5 Gene in Two Siblings with Osteoporosis-pseudoglioma Syndrome

Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder characterized by severe osteoporosis and eye abnormalities that lead to vision loss. In this study, clinical findings and genetic study of two siblings with OPPG are presented. Whole exome sequencing of DNA enriched for exonic regions was performed with SureSelect 38Mbp all exon kit v. 7.0. The two siblings presented with different clinical manifestations of OPPG. The younger female sibling had blindness and severe osteoporosis with multiple fractures, while her older brother was also blind but with less severe osteoporosis and no fractures. On analysis, a novel homozygous nonsense mutation (c.351G>A) in exon 2 of LRP5 (NM_002335) was found, predicted to change a tryptophan at 117 to a stop codon (p. Trp117Ter). Thus, a variable phenotype was associated with an identical variant in these two siblings. The novel mutation reported herein expands the spectrum of the underlying genetic pathology of OPPG.

Clinical Response to Treatment with Teriparatide in an Adolescent with Osteoporosis-Pseudoglioma Syndrome (OPPG): A Case Report.

Introduction: Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder characterized by severe osteoporosis and eye abnormalities that leads to vision loss. In this study, we report the outcome of a short period of treatment with teriparatide in one patient with OPPG. Case Presentation: The patient was a 17-year-old girl who suffered a bone fracture at the age of two and was diagnosed with OPPG at the age of three. Genetic testing was performed for the patient, and a novel homozygous nonsense mutation (c.351G>A) in exon 2 of the LRP5 gene was reported. She was treated with pamidronate, but the bone fracture increased, and the disability progressed. Therefore, at the age of 11 years and nine months, teriparatide was administered subcutaneously at a dose of 20 micrograms per day for four consecutive months. After the treatment with teriparatide, physical activity was achieved, and no further fractures were observed besides the gradual rise in bone mineral density (BMD) (from 0.532 to 0.711 gr/cm2 in lumbar spine and 0.372 to 0.635 gr/cm2 in femur neck). Conclusions: In children and adolescents diagnosed with OPPG who do not respond to other conventional therapies, short courses of teriparatide therapy may be helpful.