Lab Med Online.  2023 Apr;13(2):120-123. 10.47429/lmo.2023.13.2.120.

The First Cases of OPHN1 Exons 1 and 2 Deletion in Two X-linked Intellectual Developmental Disorder Patients in Korea

• Kim KB
• Lee S
• Kim DH

• KMID: 2552736
• DOI: http://doi.org/10.47429/lmo.2023.13.2.120

Abstract

OPHN1is located in Xq12 and acts as a regulator for the development of neural tissues in a fetus. Various spectrums of X-linked intellectual disabilities (XLIDs) can occur due to a loss of function in the OPHN1 gene. In this case study, the authors report two cases ofOPHN1-related XLID found in one family in Korea. A 7-year-old boy presented with speech development delay, intellectual disability, and an epilepsy event. There were no specific perinatal history or test results except suggestive mega cisterna magna. His younger brother had a similar phenotype. A chromosomal microarray (CMA) test showed a hemizygous 414 kbp deletion (chrX: 67,582,399-67,997,055) in both brothers, and thereafter a deletion of exons 1 and 2 of OPHN1 was confirmed via PCR. In summary, it is difficult to specify the causative gene of an intellectual disability by symptoms alone. Therefore, CMA can be used as an important diagnostic test along with tests such as whole exome sequencing.

Keyword

OPHN1; Oligophrenin-1; X-linked intellectual disability; Intellectual disability; Microarray

Figure

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  Fig. 1 The results of the CMA and PCR tests of OPHN1 exons 1–4. (A) The weighted log2 ratio and copy number state of the proband (P), his brother (B), sister (S), father (F), and mother (M). The proband and brother showed a hemizygous 414 kbp deletion (chrX: 67,582,399-67,997,055). His mother and sister had a heterozygous deletion in the same region. The father showed no abnormal findings. (B) Gel electrophoresis of the PCR products amplifying exons 1–2 of OPHN1 with the sample of the proband and family members supported the CMA findings. The proband and brother showed a complete loss of OPHN1 exons 1–2, while the mother and sister showed exons thought to be derived from conserved alleles. Primers for exons 10 of G6PD (154 bp on the band below) were used as the internal control in all the PCR tests, and ladders ranging in size from 100 to 1,300 bp were shown in the center. (C) Gel electrophoresis of the PCR products amplifying OPHN1 exons 3–4 with the sample of the proband and family members supported the CMA findings. Exons 3–4 were detected in all the family members. Abbreviation: CMA, chromosomal microarray.

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