The spectrum of 46XY disorders of sex development in a University centre in Saudi Arabia.

BACKGROUND: The term disorders of sex development (DSD) includes congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. The spectrum of the 46XY (DSD) is so broad. In this study, we reviewed the clinical spectrum of a cohort of patients with 46XY DSD in a tertiary institute in the Middle East over two decades. OBJECTIVE: To define the clinical spectrum of 46XY DSD in a major teaching hospital, Riyadh, Saudi Arabia. MATERIALS AND METHODS: This is a retrospective, case series hospital-based study. The case notes, laboratory investigations, and imaging studies were reviewed for patients with 46XY DSD over a 20 years period (1989-2010) at King Khalid University Hospital, Riyadh, Saudi Arabia. Molecular genetics were not available in all patients. RESULTS: During the period under review; a total of 56 patients were seen with 46XY DSD due to variable etiologies. Androgen insensitivity syndromes (AIS) and 5-α-reductase deficiency were among the commonest (44.6%), with multiple siblings involvement within the family. Of these, 16 patients were showing variable degrees of insensitivity ranging between complete (n=5, 31.2%) and partial (n=11, 68.8%) insensitivity, whereas in nine patients the diagnosis of 5-α-reductase deficiency was entertained based on hormonal studies. Of interest to see was a high number of patients (n=14, 25%) either with a localized congenital anomalies such as the cloacal anomalies or generalized congenital malformations following the pattern of certain syndromes. CONCLUSION: A wide spectrum of causes were noted. Androgen insensitivity syndrome was the commonest. In Saudi Arabia, where consanguineous mating is high, 5-α-reductase is also a common cause of 46XY DSD.

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.