dr. Anna Lengyel, Dr. Iren Haltrich
1 Semmelweis University 2nd Department of Pediatrics
2 Semmelweis University 2nd Department of Pediatrics
Introduction: Chromosomal abnormalities are responsible for approximately 15% of major developmental anomalies and 18% of neonatal mortality worldwide. Autosomal structural aberrations are infrequent and understood poorly.
Aim: Genotype-phenotype correlation study of a girl with an extremely rare genetic condition.
Method: Phenotype was assessed by careful exploration and physical examination. Karyotype analysis was preformed using Giemsa staining, fluorescent in situ hybridization and array comparative genomic hybridization.
Results: Her proposed G-banded karyotype was 46,XX,dup(5)(q32q34). Fluorescent in situ hybridization validated the presence of extra material on the long arm of chromosome 5 and showed that the NSD1 gene region was unaffected. Array comparative genomic hybridization localized the extra material to bands 5q23.2-q31.1 and revealed an additional duplication of region 5q13.3-q14.1.
Pure 5q duplications present with wide phenotypic variety. Our patient’s symptomatology adheres only partly with published cases. She shares low birth weight (1920 grams), minor anomalies, ventricular septal defect, strabism, muscle hypotonia and developmental delay with patients carrying overlapping duplications. Asthma is unique to her, while otherwise common traits (microcephaly, urogenital problems) are missing.
Online Mendelian Inheritance in Man database catalogues 8 disease causing genes in her two duplicated regions. Potentially relevant are PR domain-containing protein 6 (associated with patent ductus arteriosus) and Lamin B1 (duplication of this gene causes autosomal dominant adult-onset demyelinating leukodystrophy).
Conclusion: Researchers have been trying to associate specific syndromes with 5q duplications but have so far faced multiple difficulties. Refining patient karyotypes with array comparative genomic hybridization and accumulation of data are necessary for more accurate genotype-phenotype correlation studies and to better understand this particular chromosome abnormality.
The combined effect of our patient’s duplications further complicates genotype-phenotype correlation. Regular screenings are important for early recognition and treatment of potential medical problems in later life.
Doctoral School: Clinical Medicine
Program: Clinical application of basic science results
Supervisor: Iren Haltrich
E-mail address: firstname.lastname@example.org