Novel Homozygous LRP5 Mutations in Mexican Patients with Osteoporosis-Pseudoglioma Syndrome.

AIMS: Osteoporosis-pseudoglioma syndrome (OPPG) is an uncommon autosomal recessive disorder characterized by the rare association of early-onset osteoporosis and severe ocular abnormalities such as persistent fetal vasculature and microphthalmia. Biallelic mutations in the low-density lipoprotein receptor-related protein-5 gene (LRP5) have been associated with OPPG. We present clinical and genetic data from three Mexican OPPG patients, a pair of sibs, and a sporadic case. MATERIALS AND METHODS: Three patients underwent clinical examination, including a complete ophthalmic evaluation. Based on the clinical diagnosis of OPPG, the entire coding sequence of LRP5 was polymerase chain reaction-amplified and directly Sanger-sequenced. Genetic testing was extended to the parents of the affected patients. RESULTS: Phenotypic variability was observed in the familial case and molecular analysis identified a novel homozygous c.1145C>T, p.(Pro382Leu) variant in both sibs. As expected, their parents were heterozygous carriers. The sporadic patient exhibited a severe osseous phenotype, microphthalmia, and neurological symptoms. In this patient, homozygosity for the c.442C>T, p.(Gln148*) variant was demonstrated, whereas her parents were heterozygous carriers. The p.(Pro382Leu) pathogenic mutation has been previously reported only in a compound heterozygous state in OPPG patients. CONCLUSIONS: Two novel homozygous missense and nonsense variants were demonstrated in three OPPG cases from Mexico. Our results expand the spectrum of disease-causing LRP5 mutations. This is the first report of OPPG in our population and our findings may potentially add to a genotype-phenotype correlation.

Non-erosive reflux disease manifested exclusively by protracted hiccups.

Hiccups are a benign physiological feature affecting almost everyone at one time or another. They tend to be short-lived and do not affect quality of life; however, there are various pathologies that may present with long-lasting hiccups. These are grouped into 3 categories according to their duration: acute, persistent and intractable or protracted hiccups. Intractable hiccups last longer than 2 months and are usually associated with more severe conditions. The association between intractable hiccups and reflux disease has not been previously documented by objective methods. This report describes the case of a 23-year-old female who presented with protracted hiccups; all other organic pathologies were ruled out, and endoscopy and conventional pH-metry confirmed a diagnosis of non-erosive reflux disease as the unique cause.