Division of Clinical Genetics, Department of Pediatrics, Philippine General Hospital, University of the Philippines Manila, Manila, Philippines
Biochemical Genetics Laboratory, Kennedy Krieger Institute, Baltimore, Maryland, USA.
BMJ Case Rep. 2020 Nov 2;13(11):e236859. doi: 10.1136/bcr-2020-236859.
We report a case of a 1-year and 2-month-old girl with clinical features consistent with congenital hemidysplasia with ichthyosis and limb defects syndrome. Sterol analysis from skin flakes revealed increased levels of a mono 4-alpha methyl sterol also seen in plasma as well as the presence of 4-alpha-carboxy-4-methyl-cholest-8(9)-en-3beta-ol and several keto-sterols, which are usually below the limit of detection. This sterol pattern is consistent with abnormal function of the 4-alpha-methylsterol-4-demethylase complex. gene testing revealed the presence of a variant of uncertain significance, c.130G>A (p.Gly44Ser). This missense mutation currently is not included in population databases (ExAC no frequency) and has not been reported in individuals with an -related condition. Parental studies showed that neither parent carries the variant. On this basis, this variant has been reclassified as likely pathogenic. Symptomatic treatment with keratolytic agents, emollients and ketoconazole was initiated.
我们报告了一例 1 岁零 2 个月的女孩，其临床表现符合先天性偏侧肥大伴鱼鳞病和肢体缺陷综合征。皮肤鳞屑中的甾醇分析显示，一种单 4-α 甲基甾醇的水平升高，在血浆中也可见到，以及存在 4-α-羧基-4-甲基-胆甾-8(9)-烯-3β-醇和几种酮甾醇，这些通常低于检测限。这种甾醇模式与 4-α-甲基甾醇-4-脱甲基酶复合物的异常功能一致。基因检测显示存在一种意义不明的变体，c.130G>A(p.Gly44Ser)。这种错义突变目前不在人群数据库（ExAC 无频率）中，也未在与 - 相关的疾病个体中报道过。父母的研究表明，父母双方都不携带该变体。基于此，该变体已被重新分类为可能的致病性变体。开始进行角质松解剂、保湿剂和酮康唑的对症治疗。
