Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss
Multiple genome sequencing studies have identified genetic abnormalities as major causes of severe intellectual disability (ID). However, many children affected by mild ID and borderline intellectual functioning (BIF) lack a genetic diagnosis because known causative ID genetic mutations have not bee...
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1355823/full |
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| author | Haemi Choi Jeong-A. Kim Kyung-Ok Cho Kyung-Ok Cho Kyung-Ok Cho Kyung-Ok Cho Hyun Jung Kim Hyun Jung Kim Min-Hyeon Park Min-Hyeon Park |
| author_facet | Haemi Choi Jeong-A. Kim Kyung-Ok Cho Kyung-Ok Cho Kyung-Ok Cho Kyung-Ok Cho Hyun Jung Kim Hyun Jung Kim Min-Hyeon Park Min-Hyeon Park |
| author_sort | Haemi Choi |
| collection | DOAJ |
| description | Multiple genome sequencing studies have identified genetic abnormalities as major causes of severe intellectual disability (ID). However, many children affected by mild ID and borderline intellectual functioning (BIF) lack a genetic diagnosis because known causative ID genetic mutations have not been identified or the role of genetic variants in mild cases is less understood. Genetic variant testing in mild cases is necessary to provide information on prognosis and risk of occurrence. In this study, we report two sibling patients who were 5 years 9 months old and 3 years 3 months old and presented to the hospital due to developmental delay. Clinical assessment and chromosomal microarray analysis were performed. The patients were diagnosed with mild intellectual disability (ID) and borderline intellectual functioning (BIF). Genetic analysis identified a loss of 12p11.22, including the OVCH1-AS1, OVCH1, and TMTC1 genes, which was the only variant that occurred in both sisters. Identical variants were found in their father with probable BIF. Neither patient presented any brain structural abnormalities or dysmorphism, and no exogenous factors or parenting problems were reported. Thus, loss of 12p11.22 may be associated with our patients’ cognitive impairment. The OVCH1, OVCH1-AS1 and TMTC1 variants identified in this study are the most likely disease-causing genes in the sisters. Our findings may expand as yet limited knowledge on mild ID and BIF causative variants, which would further support the diagnosis even if the severity is mild. |
| first_indexed | 2024-04-24T15:27:44Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-24T15:27:44Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-69c6006916a546dbbb5c9c891618e2152024-04-02T05:24:01ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-04-011510.3389/fgene.2024.13558231355823Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 lossHaemi Choi0Jeong-A. Kim1Kyung-Ok Cho2Kyung-Ok Cho3Kyung-Ok Cho4Kyung-Ok Cho5Hyun Jung Kim6Hyun Jung Kim7Min-Hyeon Park8Min-Hyeon Park9Department of Psychiatry, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Psychiatry, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Republic of KoreaCatholic Neuroscience Institute, The Catholic University of Korea, Seoul, Republic of KoreaInstitute for Aging and Metabolic Diseases, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Psychiatry, Harvard Medical School, Boston, MA, United StatesDivision of Psychotic Disorders, McLean Hospital, Belmont, MA, United StatesDepartment of Psychiatry, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Biomedicine & Health Sciences, The Catholic University of Korea, Seoul, Republic of KoreaMultiple genome sequencing studies have identified genetic abnormalities as major causes of severe intellectual disability (ID). However, many children affected by mild ID and borderline intellectual functioning (BIF) lack a genetic diagnosis because known causative ID genetic mutations have not been identified or the role of genetic variants in mild cases is less understood. Genetic variant testing in mild cases is necessary to provide information on prognosis and risk of occurrence. In this study, we report two sibling patients who were 5 years 9 months old and 3 years 3 months old and presented to the hospital due to developmental delay. Clinical assessment and chromosomal microarray analysis were performed. The patients were diagnosed with mild intellectual disability (ID) and borderline intellectual functioning (BIF). Genetic analysis identified a loss of 12p11.22, including the OVCH1-AS1, OVCH1, and TMTC1 genes, which was the only variant that occurred in both sisters. Identical variants were found in their father with probable BIF. Neither patient presented any brain structural abnormalities or dysmorphism, and no exogenous factors or parenting problems were reported. Thus, loss of 12p11.22 may be associated with our patients’ cognitive impairment. The OVCH1, OVCH1-AS1 and TMTC1 variants identified in this study are the most likely disease-causing genes in the sisters. Our findings may expand as yet limited knowledge on mild ID and BIF causative variants, which would further support the diagnosis even if the severity is mild.https://www.frontiersin.org/articles/10.3389/fgene.2024.1355823/fullcognitive impairmentneurodevelopmental disorder12p deletionCNVchromosomal microarray analysis |
| spellingShingle | Haemi Choi Jeong-A. Kim Kyung-Ok Cho Kyung-Ok Cho Kyung-Ok Cho Kyung-Ok Cho Hyun Jung Kim Hyun Jung Kim Min-Hyeon Park Min-Hyeon Park Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss Frontiers in Genetics cognitive impairment neurodevelopmental disorder 12p deletion CNV chromosomal microarray analysis |
| title | Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss |
| title_full | Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss |
| title_fullStr | Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss |
| title_full_unstemmed | Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss |
| title_short | Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss |
| title_sort | case report intellectual disability and borderline intellectual functioning in two sisters with a 12p11 22 loss |
| topic | cognitive impairment neurodevelopmental disorder 12p deletion CNV chromosomal microarray analysis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1355823/full |
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