背景:一种罕见的常染色体隐性遗传病,3M综合征,以严重的宫内和出生后发育迟缓为特征。患有3M综合征的儿童通常表现为身材矮小,面部畸形,长管状骨,和高椎体,但通常缺乏精神异常或其他器官损伤。与3M综合征相关的致病基因包括CUL7、OBSL1和CCDC8。3M综合征患者的临床和分子特征独特,可作为重要的诊断指标。
方法:在这种情况下,病人表现出方形的肩膀,脊柱侧弯,细长的管状骨头,和正常的神经发育。值得注意的是,患者没有表现出典型的畸形面部特征,相对大头畸形,或生长迟缓通常在3M综合征个体中观察到。全外显子测序揭示了一个新的杂合c.566811G>C(剪接-3)变体和先前报道的无义杂合c.3341G>A(p。Trp1114Ter)OBSL1的变体。因此,重要的是要注意,3M综合征的临床特征可能并不总是可见的,遗传确认是经常需要的。此外,OBSL1中c.5683+1G>C变异体的鉴定值得注意,因为它以前没有在公共数据库中报道过.
结论:我们的研究确定了OBSL1的一个新变体(c.5683+1G>C),它有助于扩大3M综合征的分子谱。
BACKGROUND: A rare autosomal recessive genetic disorder, 3M syndrome, is characterized by severe intrauterine and postnatal growth retardation. Children with 3M syndrome typically exhibit short stature, facial deformities, long tubular bones, and high vertebral bodies but generally lack mental abnormalities or other organ damage. Pathogenic genes associated with 3M syndrome include CUL7, OBSL1 and CCDC8. The clinical and molecular characteristics of patient with 3M syndrome are unique and serve as important diagnostic indicators.
METHODS: In this
case, the patient displayed square shoulders, scoliosis, long slender tubular bones, and normal neurological development. Notably, the patient did not exhibit the typical dysmorphic facial features, relative macrocephaly, or growth retardation commonly observed in individuals with 3M syndrome. Whole exon sequencing revealed a novel heterozygous c.56681+1G>C (Splice-3) variant and a previously reported nonsense heterozygous c.3341G>A (p.Trp1114Ter) variant of OBSL1. Therefore, it is important to note that the clinical features of 3M syndrome may not always be observable, and genetic confirmation is often required. Additionally, the identification of the c.5683+1G>C variant in OBSL1 is noteworthy because it has not been previously reported in public databases.
CONCLUSIONS: Our study identified a new variant (c.5683+1G>C) of OBSL1 that contributes to expanding the molecular profile of 3M syndrome.