Novel Variant of the Desert Hedgehog Gene in an Indian Patient of 46, XY Gonadal Dysgenesis with Peripheral Neuropathy.

46, XY gonadal dysgenesis (GD) is rare form of sex development disorder. There have been five cases reported with 46, XY GD and mutation in Desert Hedge Hog (DHH) gene with peripheral neuropathy. To report first Indian case with 46, XY GD and severe peripheral neuropathy with a novel missense mutation in DHH gene. This is retrospective study and genetics done by clinical exome sequencing. We report a patient with primary amenorrhea and severe motor and sensory neuropathy with Charcot's joints. She presented at 30 years of age, with 15-year history of complete loss of temperature sensation and inadvertent injuries requiring amputations of toes along with distal weakness and atrophy. Ultrasound pelvis showed rudimentary structure in pelvis and absent uterus. X-ray foot showed Charcot joints. Similar neuropathy features were noted in her father and sister who also had absent uterus and ovaries. Clinical exome sequencing showed novel missense pathogenic variant (P. Ser185Pro) in exon 2 of DHH gene. This is the first case of 46, XY GD reported from India, with peripheral neuropathy and mutation in DHH gene.