Whole-exome sequencing identified a novel heterozygous variant in UBAP2L in a Chinese family with neurodevelopmental disorder characterized by impaired language, behavioral abnormalities, and dysmorphic facies
UBAP2L-deficiency syndrome, also known as neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies (NEDLBF, OMIM 620494), is an extremely rare autosomal dominant disorder. This condition is caused by heterozygous variant in the UBAP2L gene (NM_014847.4, MIM...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1503048/full |
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| author | Qi Yang Qi Yang Qiang Zhang Qiang Zhang Xunzhao Zhou Xunzhao Zhou Juntan Feng Shujie Zhang Shujie Zhang Li Lin Li Lin Shang Yi Shang Yi Zailong Qin Zailong Qin Jingsi Luo Jingsi Luo Jingsi Luo |
| author_facet | Qi Yang Qi Yang Qiang Zhang Qiang Zhang Xunzhao Zhou Xunzhao Zhou Juntan Feng Shujie Zhang Shujie Zhang Li Lin Li Lin Shang Yi Shang Yi Zailong Qin Zailong Qin Jingsi Luo Jingsi Luo Jingsi Luo |
| author_sort | Qi Yang |
| collection | DOAJ |
| description | UBAP2L-deficiency syndrome, also known as neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies (NEDLBF, OMIM 620494), is an extremely rare autosomal dominant disorder. This condition is caused by heterozygous variant in the UBAP2L gene (NM_014847.4, MIM 616472), which encodes the ubiquitin-associated protein 2-like protein involved in the formation of stress granules (SGs). To date, only one report has documented 12 loss-of-function variants in UBAP2L, all of which were identified as de novo variants. In our study, we recruited a Chinese family with two patients exhibiting intellectual disability and seizures. Whole-exome sequencing was performed on the proband, revealing a novel heterozygous frameshift variant, UBAP2L (NM_014847.4):c.2453_2454del (p.Tyr818Trpfs*3). The variant was inherited from the affected mother, and confirmed in the proband and his parents by Sanger sequencing. This is the first familial report of a deleterious UBAP2L variant. The proband in this family presented a clinical phenotype similar to NEDLBF, which includes intellectual disability, developmental delay, speech delay, facial dysmorphism, seizures, and behavioral abnormalities. The affected mother presented only mild intellectual disability and mild language impairment. By clinical evaluation of our patients and previously reported cases with UBAP2L variants, we propose that intellectual disability, developmental delay (particularly in speech), infants’ feeding difficulties, behavioural abnormalities and seizures are the main clinical features of NEDLBF patients. Our study expands the genetic and phenotypic spectrum associated with NEDLBF. |
| format | Article |
| id | doaj-art-ac44f0501d014d3dae0aa3d1af8f8cb5 |
| institution | Kabale University |
| issn | 1664-8021 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj-art-ac44f0501d014d3dae0aa3d1af8f8cb52024-12-10T06:34:05ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-12-011510.3389/fgene.2024.15030481503048Whole-exome sequencing identified a novel heterozygous variant in UBAP2L in a Chinese family with neurodevelopmental disorder characterized by impaired language, behavioral abnormalities, and dysmorphic faciesQi Yang0Qi Yang1Qiang Zhang2Qiang Zhang3Xunzhao Zhou4Xunzhao Zhou5Juntan Feng6Shujie Zhang7Shujie Zhang8Li Lin9Li Lin10Shang Yi11Shang Yi12Zailong Qin13Zailong Qin14Jingsi Luo15Jingsi Luo16Jingsi Luo17Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Pediatric Neurology, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, ChinaGuangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaDepartment of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaGuangxi Clinical Research Center for Pediatric Diseases, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, ChinaUBAP2L-deficiency syndrome, also known as neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies (NEDLBF, OMIM 620494), is an extremely rare autosomal dominant disorder. This condition is caused by heterozygous variant in the UBAP2L gene (NM_014847.4, MIM 616472), which encodes the ubiquitin-associated protein 2-like protein involved in the formation of stress granules (SGs). To date, only one report has documented 12 loss-of-function variants in UBAP2L, all of which were identified as de novo variants. In our study, we recruited a Chinese family with two patients exhibiting intellectual disability and seizures. Whole-exome sequencing was performed on the proband, revealing a novel heterozygous frameshift variant, UBAP2L (NM_014847.4):c.2453_2454del (p.Tyr818Trpfs*3). The variant was inherited from the affected mother, and confirmed in the proband and his parents by Sanger sequencing. This is the first familial report of a deleterious UBAP2L variant. The proband in this family presented a clinical phenotype similar to NEDLBF, which includes intellectual disability, developmental delay, speech delay, facial dysmorphism, seizures, and behavioral abnormalities. The affected mother presented only mild intellectual disability and mild language impairment. By clinical evaluation of our patients and previously reported cases with UBAP2L variants, we propose that intellectual disability, developmental delay (particularly in speech), infants’ feeding difficulties, behavioural abnormalities and seizures are the main clinical features of NEDLBF patients. Our study expands the genetic and phenotypic spectrum associated with NEDLBF.https://www.frontiersin.org/articles/10.3389/fgene.2024.1503048/fullUBAP2L-deficiency syndromeUBAP2Lintellectual disabilitydevelopmental delayChinese |
| spellingShingle | Qi Yang Qi Yang Qiang Zhang Qiang Zhang Xunzhao Zhou Xunzhao Zhou Juntan Feng Shujie Zhang Shujie Zhang Li Lin Li Lin Shang Yi Shang Yi Zailong Qin Zailong Qin Jingsi Luo Jingsi Luo Jingsi Luo Whole-exome sequencing identified a novel heterozygous variant in UBAP2L in a Chinese family with neurodevelopmental disorder characterized by impaired language, behavioral abnormalities, and dysmorphic facies Frontiers in Genetics UBAP2L-deficiency syndrome UBAP2L intellectual disability developmental delay Chinese |
| title | Whole-exome sequencing identified a novel heterozygous variant in UBAP2L in a Chinese family with neurodevelopmental disorder characterized by impaired language, behavioral abnormalities, and dysmorphic facies |
| title_full | Whole-exome sequencing identified a novel heterozygous variant in UBAP2L in a Chinese family with neurodevelopmental disorder characterized by impaired language, behavioral abnormalities, and dysmorphic facies |
| title_fullStr | Whole-exome sequencing identified a novel heterozygous variant in UBAP2L in a Chinese family with neurodevelopmental disorder characterized by impaired language, behavioral abnormalities, and dysmorphic facies |
| title_full_unstemmed | Whole-exome sequencing identified a novel heterozygous variant in UBAP2L in a Chinese family with neurodevelopmental disorder characterized by impaired language, behavioral abnormalities, and dysmorphic facies |
| title_short | Whole-exome sequencing identified a novel heterozygous variant in UBAP2L in a Chinese family with neurodevelopmental disorder characterized by impaired language, behavioral abnormalities, and dysmorphic facies |
| title_sort | whole exome sequencing identified a novel heterozygous variant in ubap2l in a chinese family with neurodevelopmental disorder characterized by impaired language behavioral abnormalities and dysmorphic facies |
| topic | UBAP2L-deficiency syndrome UBAP2L intellectual disability developmental delay Chinese |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1503048/full |
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