Sterol-C4-methyl oxidase (SC4MOL) deficiency was recently described as an autosomal recessive cholesterol biosynthesis disorder caused by mutations in the MSMO1 (sometimes also referred to as SC4MOL) 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>C; p.Asn27Thr in MSMO1. 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.

中文翻译：

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患有银屑病样皮炎的 SC4MOL 缺陷的两个兄弟姐妹中的新纯合错义MSMO1突变

甾醇-C4-甲基氧化酶 (SC4MOL) 缺乏症最近被描述为由 MSMO1（有时也称为 SC4MOL）基因突变引起的常染色体隐性胆固醇生物合成障碍。迄今为止，已经报告了来自 4 个无关家庭的 5 名 SC4MOL 缺乏患者。诊断可能具有挑战性，因为甲基甾醇的生化积累会影响全球发育并导致皮肤和眼部病变。在此，我们描述了来自土耳其血缘家庭的 2 名兄弟姐妹，他们患有 SC4MOL 缺乏症，表现为银屑病样皮炎、眼部异常（眼球震颤、视神经发育不全、近视和斜视）、严重的智力障碍以及生长和运动发育迟缓。我们进行了全外显子组测序，发现了一个新的纯合错义突变 c.81A>C；MSMO1 中的 p.Asn27Thr。所有可用家庭成员的分离分析证实了突变的隐性遗传。这对兄弟姐妹接受了口服和局部他汀类药物和胆固醇的联合治疗，导致临床改善。这项研究展示了基于基因组学的诊断和治疗如何有助于临床实践。