{"title":"土耳其范可尼贫血家族中alu介导的FANCA缺失:奠基者效应的证据","authors":"Ceren Damla Durmaz, Fatma Gümrük, Tiraje Celkan, Sule Unal, Arda Çetinkaya","doi":"10.1002/ajmg.a.63945","DOIUrl":null,"url":null,"abstract":"<p><p>Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome characterized by pancytopenia, increased susceptibility to malignancies, and a spectrum of congenital anomalies. Here, we report on eight affected individuals from six unrelated families with a large Alu-mediated intragenic deletion encompassing exons 6-31 in the FANCA gene, identified as a founder mutation in the Turkish population through haplotype analysis. This deletion, mediated by Alu repeat sequences, underscores the role of repetitive elements in FA pathogenesis. Clinical data revealed variable phenotypic presentations among affected individuals, highlighting the challenge of establishing genotype-phenotype correlations even in the presence of identical FANCA pathogenic variants. We carried out an easy and effective PCR-based diagnostic test for detecting this mutation, enabling precise diagnosis and genetic counseling for affected individuals and their families. This study provides valuable insights into the molecular mechanisms underlying FA pathogenesis and offers a practical approach for genetic diagnosis in affected individuals, particularly those of Turkish descent.</p>","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":" ","pages":"e63945"},"PeriodicalIF":1.7000,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Alu-Mediated Deletion of FANCA in Turkish Families With Fanconi Anemia: Evidence of a Founder Effect.\",\"authors\":\"Ceren Damla Durmaz, Fatma Gümrük, Tiraje Celkan, Sule Unal, Arda Çetinkaya\",\"doi\":\"10.1002/ajmg.a.63945\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome characterized by pancytopenia, increased susceptibility to malignancies, and a spectrum of congenital anomalies. Here, we report on eight affected individuals from six unrelated families with a large Alu-mediated intragenic deletion encompassing exons 6-31 in the FANCA gene, identified as a founder mutation in the Turkish population through haplotype analysis. This deletion, mediated by Alu repeat sequences, underscores the role of repetitive elements in FA pathogenesis. Clinical data revealed variable phenotypic presentations among affected individuals, highlighting the challenge of establishing genotype-phenotype correlations even in the presence of identical FANCA pathogenic variants. We carried out an easy and effective PCR-based diagnostic test for detecting this mutation, enabling precise diagnosis and genetic counseling for affected individuals and their families. This study provides valuable insights into the molecular mechanisms underlying FA pathogenesis and offers a practical approach for genetic diagnosis in affected individuals, particularly those of Turkish descent.</p>\",\"PeriodicalId\":7507,\"journal\":{\"name\":\"American Journal of Medical Genetics Part A\",\"volume\":\" \",\"pages\":\"e63945\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-12-03\",\"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.63945\",\"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.63945","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Alu-Mediated Deletion of FANCA in Turkish Families With Fanconi Anemia: Evidence of a Founder Effect.
Fanconi anemia (FA) is a rare inherited bone marrow failure syndrome characterized by pancytopenia, increased susceptibility to malignancies, and a spectrum of congenital anomalies. Here, we report on eight affected individuals from six unrelated families with a large Alu-mediated intragenic deletion encompassing exons 6-31 in the FANCA gene, identified as a founder mutation in the Turkish population through haplotype analysis. This deletion, mediated by Alu repeat sequences, underscores the role of repetitive elements in FA pathogenesis. Clinical data revealed variable phenotypic presentations among affected individuals, highlighting the challenge of establishing genotype-phenotype correlations even in the presence of identical FANCA pathogenic variants. We carried out an easy and effective PCR-based diagnostic test for detecting this mutation, enabling precise diagnosis and genetic counseling for affected individuals and their families. This study provides valuable insights into the molecular mechanisms underlying FA pathogenesis and offers a practical approach for genetic diagnosis in affected individuals, particularly those of Turkish descent.
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 .