Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities [version 1; referees: 2 approved]
Microcephaly is a fairly common feature observed in children with delayed development, defined as head circumference less than 2 standard deviations below the mean for age and gender. It may be the result of an acquired insult to the brain, such prenatal or perinatal brain injury (congenital infecti...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2015-09-01
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| Online Access: | http://f1000research.com/articles/4-912/v1 |
| _version_ | 1819295282122194944 |
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| author | Mohan Narayanan Keri Ramsey Theresa Grebe Isabelle Schrauwen Szabolcs Szelinger Matthew Huentelman David Craig Vinodh Narayanan C4RCD Research Group |
| author_facet | Mohan Narayanan Keri Ramsey Theresa Grebe Isabelle Schrauwen Szabolcs Szelinger Matthew Huentelman David Craig Vinodh Narayanan C4RCD Research Group |
| author_sort | Mohan Narayanan |
| collection | DOAJ |
| description | Microcephaly is a fairly common feature observed in children with delayed development, defined as head circumference less than 2 standard deviations below the mean for age and gender. It may be the result of an acquired insult to the brain, such prenatal or perinatal brain injury (congenital infection or hypoxic ischemic encephalopathy), or be a part of a genetic syndrome. There are over 1000 conditions listed in OMIM (Online Mendelian Inheritance in Man) where microcephaly is a key finding; many of these are associated with specific somatic features and non-CNS anomalies. The term primary microcephaly is used when microcephaly and delayed development are the primary features, and they are not part of another recognized syndrome. In this case report, we present the clinical features of siblings (brother and sister) with primary microcephaly and delayed development, and subtle dysmorphic features. Both children had brain MRI studies that showed periventricular and subcortical T2/FLAIR hyperintensities, without signs of white matter volume loss, and no parenchymal calcifications by CT scan. The family was enrolled in a research study for whole exome sequencing of probands and parents. Analysis of variants determined that the children were compound heterozygotes for nonsense mutations, c.277C>T (p.Arg93*) and c.397C>T (p.Arg133*), in the TRMT10A gene. Mutations in this gene have only recently been reported in children with microcephaly and early onset diabetes mellitus. Our report adds to current knowledge of TRMT10A related neurodevelopmental disorders and demonstrates imaging findings suggestive of delayed or abnormal myelination of the white matter in this disorder. Accurate diagnosis through genomic testing, as in the children described here, allows for early detection and management of medical complications, such as diabetes mellitus. |
| first_indexed | 2024-12-24T04:39:44Z |
| format | Article |
| id | doaj.art-826d38009a394689a4d1e542a1cbf769 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-24T04:39:44Z |
| publishDate | 2015-09-01 |
| publisher | F1000 Research Ltd |
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| spelling | doaj.art-826d38009a394689a4d1e542a1cbf7692022-12-21T17:14:53ZengF1000 Research LtdF1000Research2046-14022015-09-01410.12688/f1000research.7106.17652Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities [version 1; referees: 2 approved]Mohan Narayanan0Keri Ramsey1Theresa Grebe2Isabelle Schrauwen3Szabolcs Szelinger4Matthew Huentelman5David Craig6Vinodh Narayanan7C4RCD Research GroupBarrow Neurological Institute, Phoenix, AZ, USANeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USADepartment of Genetics, Phoenix Children’s Hospital, Phoenix, AZ, USANeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USANeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USANeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USANeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USANeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USAMicrocephaly is a fairly common feature observed in children with delayed development, defined as head circumference less than 2 standard deviations below the mean for age and gender. It may be the result of an acquired insult to the brain, such prenatal or perinatal brain injury (congenital infection or hypoxic ischemic encephalopathy), or be a part of a genetic syndrome. There are over 1000 conditions listed in OMIM (Online Mendelian Inheritance in Man) where microcephaly is a key finding; many of these are associated with specific somatic features and non-CNS anomalies. The term primary microcephaly is used when microcephaly and delayed development are the primary features, and they are not part of another recognized syndrome. In this case report, we present the clinical features of siblings (brother and sister) with primary microcephaly and delayed development, and subtle dysmorphic features. Both children had brain MRI studies that showed periventricular and subcortical T2/FLAIR hyperintensities, without signs of white matter volume loss, and no parenchymal calcifications by CT scan. The family was enrolled in a research study for whole exome sequencing of probands and parents. Analysis of variants determined that the children were compound heterozygotes for nonsense mutations, c.277C>T (p.Arg93*) and c.397C>T (p.Arg133*), in the TRMT10A gene. Mutations in this gene have only recently been reported in children with microcephaly and early onset diabetes mellitus. Our report adds to current knowledge of TRMT10A related neurodevelopmental disorders and demonstrates imaging findings suggestive of delayed or abnormal myelination of the white matter in this disorder. Accurate diagnosis through genomic testing, as in the children described here, allows for early detection and management of medical complications, such as diabetes mellitus.http://f1000research.com/articles/4-912/v1Diabetes & ObesityGenomics |
| spellingShingle | Mohan Narayanan Keri Ramsey Theresa Grebe Isabelle Schrauwen Szabolcs Szelinger Matthew Huentelman David Craig Vinodh Narayanan C4RCD Research Group Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities [version 1; referees: 2 approved] F1000Research Diabetes & Obesity Genomics |
| title | Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities [version 1; referees: 2 approved] |
| title_full | Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities [version 1; referees: 2 approved] |
| title_fullStr | Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities [version 1; referees: 2 approved] |
| title_full_unstemmed | Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities [version 1; referees: 2 approved] |
| title_short | Case Report: Compound heterozygous nonsense mutations in TRMT10A are associated with microcephaly, delayed development, and periventricular white matter hyperintensities [version 1; referees: 2 approved] |
| title_sort | case report compound heterozygous nonsense mutations in trmt10a are associated with microcephaly delayed development and periventricular white matter hyperintensities version 1 referees 2 approved |
| topic | Diabetes & Obesity Genomics |
| url | http://f1000research.com/articles/4-912/v1 |
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