Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5‐year‐old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole‐exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen‐magnetic resonance spectroscopy (H‐MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7‐related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth.

中文翻译：

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患有新型MBOAT7变体的患者：小脑萎缩是进行性的，并表现出特殊的神经代谢特征。

已经在属于18个家庭的43位患者中描述了MBOAT7基因的突变，这些突变显示出非特异性的临床特征（智力障碍[ID]，癫痫发作，小头畸形或大头畸形，以及轻度至中度小脑萎缩），这使临床诊断变得困难。在这里，我们报道了第一例意大利患者，即一位22.5岁的女性，是据报道年龄最大的一位，她的母亲显然是近亲的。她表现出严重的ID，大头畸形，癫痫发作，剧烈爆发，食欲亢进。我们也是在记录小脑蚓部的逐步萎缩，这似乎不是7.鉴定了新的变异纯合子c.1057_1058delGCinsCA（p.Ala353His）三人的全基因组测序岁之前MBOAT7基因。该变体被认为可能是致病的，因为它在种群数据库中不存在，并且位于一个高度保守的氨基酸残基中。该疾病具有神经代谢的发病机制，涉及磷脂重塑异常。我们患者的脑氢磁共振波谱（H-MRS）检查显示小脑半球区域有特殊的神经代谢特征。这一新发现可能解决与ID和小脑萎缩相关的广泛遗传疾病中MBOAT7相关疾病的临床怀疑。而且，有记录的小脑萎缩的进展和疾病的恶化仅在几年后才打开，有可能在出生后出现治疗窗口。