A novel pathogenic mutation of the CYP27B1 gene in a patient with vitamin D-dependent rickets type 1: a case report

BACKGROUND: Rickets can occur due to Vitamin D deficiency or defects in its metabolism. Three rare genetic types of rickets with different alterations of genes have been reported, including: Vitamin D dependent rickets type 1, Vitamin D dependent rickets type 2 or also known as Vitamin D resistant rickets and 25 hydroxylase deficiency rickets. Vitamin D dependent rickets type 1 is inherited in an autosomal recessive pattern, and is caused by mutations in the CYP27B1 gene encoding the 1α-hydroxylase enzyme. We report here a new mutation in CYP27B1, which lead to Vitamin D dependent rickets type 1. CASE PRESENTATION: We report on a 13-month-old Arabic Saudi girl with Vitamin D dependent rickets type 1 presented with multiple fractures and classic features of rickets. A whole exome sequencing identified a novel pathogenic missense mutation (CYP27B1:Homozygous c.1510C > T(p.Q504X)) which results in a protein truncating alteration. Both parents are heterozygous carriers of the mutation. Based on data search in Human Gene Mutation Database, 63 CYP27B1 alterations were reported: only 28.6% are protein truncating (5 nonsense, 13 frameshift insertions/deletions, 0 gross deletions), while 61.9% are non-truncating (38 missense, 1 small in-frame insertions/deletion), and 9.5% are possible protein-truncating (5 splice, 1 regulatory). CONCLUSION: The deleterious effect of this alteration, which was the only mutation detected in the CYP27B1 common gene of Vitamin D dependent rickets type 1 in the proband, and its autosomal recessive inheritance fashion, both support a pathogenic nature of this mutation as the cause of Vitamin D dependent rickets type 1

Disorders of Sex Development: Diagnostic Approaches and Management Options— An Islamic Perspective

Ambiguous genitalia, currently defined as disorders of sex development (DSD), are not uncommon in the Muslim community. DSD constitute a complex, major social and medical emergency, as several forms of congenital adrenal hyperplasia can lead to significant salt loss, which may lead to shock if unrecognised and not appropriately treated. To ensure that the affected individual has a high quality of life (a successful outcome), medical practitioners must quickly and correctly assign the individual’s gender and effectively assuage the family’s concerns and anxieties. It is important to review and understand the embryology and physiology of sexual differentiation, and to understand the various aetiological causes of sexual ambiguity. In this review, the diagnostic approach and management of ambiguous genitalia is thoroughly discussed from an Islamic point of view

Childhood Gynecomastia: A Mini Review

Gynecomastia, referred to enlargement of the male’s breast tissue is a common finding in boys during childhood. Although most cases are benign and self-limited, it may be a sign of an underlying systemic disease or even drug induced. Rarely, it may represent male breast cancer. Understanding its pathogenesis is crucial to distinguish a normal developmental variant from pathological cases.This review will highlight the pathophysiology, etiology, diagnosis and various medical and surgical therapies.</p