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

ISSN 2347-954X (Print) Radiologic Imaging in Patients with 46 XY, Disorders of Sex Development (DSD): A 25 Years' Experience from a Major Teaching Hospital

Abstract: Disorders of sex development (DSD), is a group of conditions where the external genitalia appear abnormal. It represents a true medical and social emergency which need a multi-disciplinary team approach for elucidation. The pediatric radiologist plays an important role in defining the genital anatomy which remains one of the most important factors in sex determination, in addition to chromosomal analysis. It was a retrospective hospital-based study, conducted over 25 years between January 1989 and December 2014. Imaging studies (ultrasound, and/or magnetic resonance imaging were retrospectively reviewed in various patients with 46XY, DSD confirmed by chromosomal analysis and appropriate hormonal investigations. Fifty-six patients were diagnosed to have 46 XY, disorders of sex development (DSD), with variable etiological causes with androgen insensitivity and 5--reductase deficiency were among the commonest. In addition to radiological, hormonal and chromosomal studies, laparoscopy studies were needed in four patients. Ultrasound was the primary modality for screening, as it is so sensitive and specific for eliciting the presence or absence of internal organs, but it less sensitive in identifying the testes, only 6 out of 18 (33.3%) patients and operator dependent. However, Magnetic Resonance (MRI) was more sensitive for testicular tissue identification reaching up to 100%, and can detail various internal structures. At the time of diagnosis of 46 XY, DSD, imaging to characterize the pelvic structures should be ordered. Ultrasound continues to remain the first choice for initial evaluation, as it is cheap, easily accessible and has a high sensitivity and specificity for eliciting the presence or absence of female internal organ; however, it is less sensitive in identifying the tests and is operator dependent. Magnetic resonance (MRI) has been used as a helpful modality for difficult cases as it is more sensitive for testicular tissue identification, and can detailed internal structure