First case of desmosterolosis diagnosed by prenatal whole exome sequencing.
Hill, Chloe Noureldein, Mona Karkhanis, Pallavi Kinning, Esther Vijay, Suresh Gowda, Harsha
Hill, Chloe
Noureldein, Mona
Karkhanis, Pallavi
Kinning, Esther
Vijay, Suresh
Gowda, Harsha
Abstract
Desmosterolosis is a rare autosomal recessive disorder of cholesterol biosynthesis resulting in multiple congenital abnormalities and syndromic intellectual disability. It is caused by defects in DHCR24, the gene encoding 3-β-hydroxysterol-24-reductase (24-dehydrocholesterol reductase), which acts in conversion of cholesterol precursor desmosterol, hence resulting in elevated plasma desmosterol levels. To date, desmosterolosis has been reported in 10 patients. Here we report an eleventh patient with desmosterolosis, and the first one to be diagnosed antenatally. Diagnosis was made on whole exome sequencing after amniocentesis due to complex antenatal abnormalities including cerebellar hypoplasia, microgyria, aortic stenosis, and renal tract abnormalities. Sterol quantitation was subsequently done postnatally, which supported the diagnosis. Although the nonspecific features make desmosterolosis difficult to suspect, we demonstrate that disorders of cholesterol synthesis can be considered as a differential diagnosis antenatally.
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Date
2022-12-20
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Hill C, Noureldein M, Karkhanis P, Kinning E, Vijay S, Gowda H. First case of desmosterolosis diagnosed by prenatal whole exome sequencing. Am J Med Genet A. 2023 Mar;191(3):859-863. doi: 10.1002/ajmg.a.63083. Epub 2022 Dec 20