Najlaa A Alsubeeh, Mohammed A Almuqbil, William Davies, Aida Bertoli-Avella, Swathi Anikar, Emir Zonic, Wafaa M Eyaid
{"title":"CCDC47 基因与三肝神经发育综合征:沙特阿拉伯第五和第六例病例报告。","authors":"Najlaa A Alsubeeh, Mohammed A Almuqbil, William Davies, Aida Bertoli-Avella, Swathi Anikar, Emir Zonic, Wafaa M Eyaid","doi":"10.1002/ajmg.a.63784","DOIUrl":null,"url":null,"abstract":"<p><p>Trichohepatoneurodevelopmental syndrome (THNS) is an ultra-rare and complex disorder affecting multiple organ systems. It is characterized by liver dysfunction, hypotonia, global developmental delay, coarse hair, and dysmorphic features. We describe two cases of THNS of Saudi origin, the fifth and sixth cases in the medical literature. Both cases presented with multiple dysmorphic features, generalized hypotonia, global developmental delay, and high liver enzyme level. Exome sequencing of Case 1 identified a pathogenic homozygous variant within the CCDC47: NM_020198.2:c.567_570del, p.(Glu190Profs*7). Genome sequencing of Case 2 identified two likely pathogenic heterozygous variants within the CCDC47: NM_020198.2:c.1327C>T, p.(Arg443*) and NM_020198.2:c.422dup, p.(Leu141Phefs*19). The trans phase of the detected variants has been confirmed by the parental testing. Furthermore, we evaluated the gene-disease association as per ClinGen guidelines and reached a strong level of association after inclusion of the new patients/variants. The findings from these cases will help to delineate the clinical phenotype and the mutational spectrum of this complex disorder.</p>","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":null,"pages":null},"PeriodicalIF":1.7000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"CCDC47 gene and trichohepatoneurodevelopmental syndrome: Report of the fifth and sixth cases from Saudi Arabia.\",\"authors\":\"Najlaa A Alsubeeh, Mohammed A Almuqbil, William Davies, Aida Bertoli-Avella, Swathi Anikar, Emir Zonic, Wafaa M Eyaid\",\"doi\":\"10.1002/ajmg.a.63784\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Trichohepatoneurodevelopmental syndrome (THNS) is an ultra-rare and complex disorder affecting multiple organ systems. It is characterized by liver dysfunction, hypotonia, global developmental delay, coarse hair, and dysmorphic features. We describe two cases of THNS of Saudi origin, the fifth and sixth cases in the medical literature. Both cases presented with multiple dysmorphic features, generalized hypotonia, global developmental delay, and high liver enzyme level. Exome sequencing of Case 1 identified a pathogenic homozygous variant within the CCDC47: NM_020198.2:c.567_570del, p.(Glu190Profs*7). Genome sequencing of Case 2 identified two likely pathogenic heterozygous variants within the CCDC47: NM_020198.2:c.1327C>T, p.(Arg443*) and NM_020198.2:c.422dup, p.(Leu141Phefs*19). The trans phase of the detected variants has been confirmed by the parental testing. Furthermore, we evaluated the gene-disease association as per ClinGen guidelines and reached a strong level of association after inclusion of the new patients/variants. The findings from these cases will help to delineate the clinical phenotype and the mutational spectrum of this complex disorder.</p>\",\"PeriodicalId\":7507,\"journal\":{\"name\":\"American Journal of Medical Genetics Part A\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Medical Genetics Part A\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1002/ajmg.a.63784\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Medical Genetics Part A","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/ajmg.a.63784","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
CCDC47 gene and trichohepatoneurodevelopmental syndrome: Report of the fifth and sixth cases from Saudi Arabia.
Trichohepatoneurodevelopmental syndrome (THNS) is an ultra-rare and complex disorder affecting multiple organ systems. It is characterized by liver dysfunction, hypotonia, global developmental delay, coarse hair, and dysmorphic features. We describe two cases of THNS of Saudi origin, the fifth and sixth cases in the medical literature. Both cases presented with multiple dysmorphic features, generalized hypotonia, global developmental delay, and high liver enzyme level. Exome sequencing of Case 1 identified a pathogenic homozygous variant within the CCDC47: NM_020198.2:c.567_570del, p.(Glu190Profs*7). Genome sequencing of Case 2 identified two likely pathogenic heterozygous variants within the CCDC47: NM_020198.2:c.1327C>T, p.(Arg443*) and NM_020198.2:c.422dup, p.(Leu141Phefs*19). The trans phase of the detected variants has been confirmed by the parental testing. Furthermore, we evaluated the gene-disease association as per ClinGen guidelines and reached a strong level of association after inclusion of the new patients/variants. The findings from these cases will help to delineate the clinical phenotype and the mutational spectrum of this complex disorder.
期刊介绍:
The American Journal of Medical Genetics - Part A (AJMG) gives you continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as in-depth documentation of phenotype analysis within the current context of genotype/phenotype correlations. In addition to Part A , AJMG also publishes two other parts:
Part B: Neuropsychiatric Genetics , covering experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders.
Part C: Seminars in Medical Genetics , guest-edited collections of thematic reviews of topical interest to the readership of AJMG .