Exome Sequencing in Monogenic Forms of Rickets.

OBJECTIVE: To understand the phenotypic and genotypic spectrum of genetic forms of rickets in 10 families. METHODS: Detailed clinical, radiographic, and biochemical evaluation of 10 families with phenotypes suggestive of a genetic cause of rickets was performed. Molecular testing using exome sequencing aided in the diagnosis of six different forms of known genetic causes. RESULTS: Eleven disease-causing variants including five previously reported variants (CYP27B1:c.1319_1325dup, p.(Phe443Profs*24), VDR:c.1171C>T, p.(Arg391Cys), PHEX: c.1586_1586+1del, PHEX: c.1482+5G>C, PHEX: c.58C>T, p.(Arg20*)) and six novel variants (CYP27B1:c.974C>T, p.(Thr325Met), CYP27B1: c.1376G>A, p.(Arg459His), CYP2R1: c.595C>T, p.(Arg199*), CYP2R1:c.1330G>C, p.(Gly444Arg),SLC34A3:c.1336-11_1336-1del, SLC2A2: c.589G>C, p.(Val197Leu)) in the genes known to cause monogenic rickets were identified. CONCLUSION: The authors hereby report a case series of individuals from India with a molecular diagnosis of rickets and provide the literature review which would help in enhancing the clinical and molecular profile for rapid and differential diagnosis of rickets.

Assessing the quality of life in Indian Graves' orbitopathy patients and validation of Hindi version of GO-QOL questionnaire.

Purpose: To validate the GO-specific quality of life (QOL) questionnaire in Hindi language and to determine the correlation of scores (visual functioning and appearance) with disease severity and activity. Methods: We recruited 114 consecutive patients with GO attending Endocrinology Clinic at tertiary care center. Eye examination was performed, and QOL was assessed by questionnaire. Results: The questionnaire was validated by 50 GO patients and test-retest reliability was performed in 15 patients. Hindi version GO-QOL was administered in 49 GO patients. GO was mild in 51.0% and sight-threatening in only 2.0% of cases. Orbitopathy was clinically active in only 10 (20.4%) cases. The GO-QOL scores (median) for visual function and appearance were 81.3 and 62.5, respectively. Patients with moderate-to-severe and sight-threatening GO had significantly lower median appearance scores (56.3 vs. 68.5, P= 0.01) compared to mild disease but no difference in visual scores. Patients with active disease had significant lower median visual function (53.1 vs. 85.7, P= 0.009) and psychosocial (appearance) scores (40.6 vs. 68.8, P= 0.03) compared to inactive disease. On multivariate regression analysis of GO-QOL scores, extraocular eye movement involvement (EOM), proptosis, and severity of eye disease were significantly associated with visual functioning while appearance was significantly associated only with the severity of eye disease. Conclusion: GO-QOL scores were significantly reduced in patients with GO.