Case presentation
A 2-years-old male proband (figure 1a, 1b)was diagnosed with severe intellectual disability. However, we did not find chromosome abnormality or the abnormal number of chromosomes. Notably, only one mutation of the patient was found by whole-exome sequencing,which was a novel UBE2A splice site mutation (c.241+1 G>A) (figure 2a, 2b). This splice site mutation was not previously reported or annotated in any public databases,and it modified one nucleotide near exon 4 (figure 3a), likely influencing its splicing. Similarly, the splice site mutation was assessed with a pathogenic criterion (PVS1). His parents without mental retardation were examined by whole-exome sequencing, and the results indicated that the boy had inherited 241+1 G>A mutation from his mother (Figure 2a).
The proband was born in the 35th week of gestation with a birth weight of 2150 g as the first child of a healthy, non-consanguineous couple of Chinese descent. After born by cesarean section due to fetal hypoxia, the infant was admitted to the neonatal intensive care unit for 28 days because of hypoxia and premature delivery.according to his parents. Four-dimensional color doppler of gestation age 34+4w showed stricture of the aortic arch, isthmus narrowing, abnormal shape of the umbilical vein, higher the systolic-diastolic ratio (S/D) of the umbilical artery, poor S/D, and pulsatility index (PI) of the middle cerebral artery. Normal fetal karyotype was examined by using umbilical cord blood.
A male proband at the age of 7 months, was consulted in the Changsha Hospital for Maternal&Child Health Care after initial symptoms were detected and which were characterized by still erected head unstable and frequent receded head. Thus, he was examined by Gesell’s infant development scale score (Gesell) to 12, whereas Gesell’s score < 25 indicates very severe neurological damage [13]. The facial appearance included a wide round face, ocular hypertelorism, short hands and feet, and a typical four-finger line [14] (figure 1a, 1b). Brain magnetic resonance image (MRI) performed abnormal signal changes in the deep white matter area near the lateral ventricle and mild delay of myelination compared to a healthy child at the age of 7 months (Figure 4).