Ghoumid Jamal, Petit Florence, Boute-Benejean Odile, Frenois Frédéric, Cartigny Maryse, Vanlerberghe Clémence, Smol Thomas, Caumes Roseline, de Roux Nicolas, Manouvrier-Hanu Sylvie
Service de Génétique Clinique, Hôpital Jeanne de Flandre, CHU Lille, Lille, France.
EA7364 RADEME (Research Team on Rare Developmental and Metabolic Diseases), Université Lille 2, Lille, France.
Eur J Hum Genet. 2017 Aug;25(8):1011-1014. doi: 10.1038/ejhg.2017.73. Epub 2017 Jun 7.
CHES (cerebellar hypoplasia with endosteal sclerosis) syndrome (OMIM#213002) associates hypomyelination, cerebellar atrophy, hypogonadism and hypodontia. So far, only five patients have been described. The condition is of neonatal onset. Patients have severe psychomotor delay and moderate to severe intellectual disability. Inheritance is assumed to be autosomal recessive due to recurrence in sibs, consanguinity of parents and absence of vertical transmission. CHES syndrome is reminiscent of 4H-leukodystrophy, a recessive-inherited affection due to variations in genes encoding subunits of the RNA polymerase III (POLR3A-POLR3B-POLR1C). POLR3B variants have been identified in one CHES patient. Here we report on a novel CHES patient, carrying compound heterozygous variations in POLR3B. This report confirms affiliation of CHES to POLR3-related disorders and suggests that CHES syndrome represents a severe form of 4H-leukodystrophy.
CHES（伴有骨内膜硬化的小脑发育不全）综合征（OMIM#213002）伴有髓鞘形成不足、小脑萎缩、性腺功能减退和牙发育不全。到目前为止，仅描述了5例患者。该病于新生儿期发病。患者有严重的精神运动发育迟缓以及中度至重度智力残疾。由于同胞复发、父母近亲结婚且无垂直遗传，推测其遗传方式为常染色体隐性遗传。CHES综合征让人联想到4H-脑白质营养不良，这是一种由于编码RNA聚合酶III（POLR3A - POLR3B - POLR1C）亚基的基因变异导致的隐性遗传疾病。在1例CHES患者中已鉴定出POLR3B变异。在此，我们报告1例新的CHES患者，其携带POLR3B的复合杂合变异。本报告证实了CHES与POLR3相关疾病的关联，并表明CHES综合征代表了4H-脑白质营养不良的一种严重形式。
