New Homozygous Missense <b><i>MSMO1</i></b> Mutation in Two Siblings with SC4MOL Deficiency Presenting with Psoriasiform Dermatitis

Abstract

Sterol-C4-methyl oxidase (SC4MOL) deficiency was recently described as an autosomal recessive cholesterol biosynthesis disorder caused by mutations in the &lt;i&gt;MSMO1&lt;/i&gt; (sometimes also referred to as &lt;i&gt;SC4MOL&lt;/i&gt;) gene. To date, 5 patients from 4 unrelated families with SC4MOL deficiency have been reported. Diagnosis can be challenging as the biochemical accumulation of methylsterols can affect global development and cause skin and ocular pathology. Herein, we describe 2 siblings from a consanguineous Turkish family with SC4MOL deficiency presenting with psoriasiform dermatitis, ocular abnormalities (nystagmus, optic hypoplasia, myopia, and strabismus), severe intellectual disability, and growth and motor delay. We undertook whole-exome sequencing and identified a new homozygous missense mutation c.81A&amp;#x3e;C; p.Asn27Thr in &lt;i&gt;MSMO1&lt;/i&gt;. Segregation analysis in all available family members confirmed recessive inheritance of the mutation. The siblings were treated with a combination of oral and topical statin and cholesterol which resulted in clinical improvement. This study demonstrates how genomics-based diagnosis and therapy can be helpful in clinical practice.

Down-regulation of MSMO1 promotes the development and progression of pancreatic cancer

“…MSMO1, as a typical target in cholesterol biosynthesis, catalyzes the demethylation of C4-methylsterol in the cholesterol synthesis pathway and plays a key role in the normal synthesis of cholesterol 9 , 16 . Recently, MSMO1 is considered as a novel and critical gene target in various solid cancers, including breast cancer 11 , oligodendroglia cells 12 , hypopharyngeal cancer 17 , gastric cancer 18 , uveal melanoma 19 , liver cancer 20 and cervical squamous cell carcinoma 21 .…”

“…Increasing evidence confirms the significant role of PI3K-AKT-mTOR signaling pathway and it's downstream targets (p-AKT, p-PI3K and p-mTOR) in regulating EMT process 7 , 8 . Methylsterol monooxygenase 1 (MSMO1), as a synonym for sterol-C4-methyl oxidase analog (SC4MOL), displays critical function in the normal synthesis of cholesterol 9 . Recently, MSMO1 has been reported to promote the development of various cancers including liver 10 , breast 11 , and oligodendroglioma 12 .…”

Differences in gene expression and variable splicing events of ovaries between large and small litter size in Chinese Xiang pigs

“…As the receptor of HDL, SCARB1 participates in the optional absorption of cholesteryl ether together with the transport outside of HDL-dependent cholesterol, and even accelerates the flow of esterified or free cholesterol on cell surface together with modified lipoproteins [ 40 ]. MSMO1 takes part in the first reaction to remove the two C-4 methyl from molecule 4, 4-dimethylzymosterol [ 41 ].…”

Clinical characterization of a new individual with mild SC4MOL deficiency: diagnostic and therapeutic implications

“…The first individual with SC4MOL deficiency was described in 2011; only seven additional cases from five unrelated families have been reported since [6,7,10,11] . Based on these reports, the most characteristic clinical features of SC4MOL deficiency include the triad of microcephaly, congenital cataracts, and psoriatic dermatitis (MCCPD), followed by delayed growth and puberty, developmental delay, and intellectual disability.…”

“…Based on these reports, the most characteristic clinical features of SC4MOL deficiency include the triad of microcephaly, congenital cataracts, and psoriatic dermatitis (MCCPD), followed by delayed growth and puberty, developmental delay, and intellectual disability. Reported biochemical abnormalities consist of increased levels of 4-monomethyl and 4,4′-dimethyl sterols in plasma from all five patients from whom cholesterol precursor levels were evaluated, in addition to decreased total cholesterol level in two cases [6,10] .…”