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Three cases with de novo 6q imbalance and variable prenatal phenotype
Francesca R Grati1, Faustina Lalatta, Licia Turolla
1Dipartimento di Medicina, Chirurgia ed Odontoiatria, Genetica Medica, Università degli Studi di Milano, Milano, Italia.
American Journal of Medical Genetics. Part A
|June 16, 2005
Summary
De novo 6q chromosomal imbalances in fetuses can cause diverse abnormal phenotypes, including arthrogryposis and growth restriction. These paternal rearrangements highlight chromosome 6q as a fragile site, necessitating genetic counseling and prenatal diagnosis for recurrence risks.
Area of Science:
- Genetics
- Developmental Biology
- Human Genetics
Background:
- Chromosomal abnormalities are a significant cause of congenital anomalies.
- De novo rearrangements, occurring without parental inheritance, present unique challenges in genetic counseling.
- The long arm of chromosome 6 (6q) is implicated in various genetic disorders.
Observation:
- Three fetuses across two families presented with de novo 6q imbalances and distinct abnormal phenotypes.
- Case 1 exhibited a complex rearrangement with deletions and duplications on 6q, leading to arthrogryposis, joint contractures, and a short neck.
- Case 2 showed a de novo 6q21 deletion associated with intrauterine growth restriction (IUGR) and agenesis of the ductus venosus.
- Case 3 had a de novo 6q14-q16 deletion with minor facial anomalies and limb contractures.
Findings:
- Segregation analysis using short tandem repeats (STRs) confirmed de novo alterations and determined their paternal origin.
- The observed phenotypes, including arthrogryposis, IUGR, and contractures, are consistent with previously reported 6q imbalances.
- The study suggests chromosome arm 6q may be particularly susceptible to rearrangements, resulting in a spectrum of heterogeneous phenotypes.
Implications:
- The findings underscore the potential for recurrent chromosomal imbalances in consecutive pregnancies within families, as seen in family A.
- Genetic counseling for such cases must address the possibility of recurrence and recommend early prenatal diagnosis for subsequent pregnancies.
- This research contributes to understanding the genotype-phenotype correlations associated with 6q alterations and informs reproductive decision-making.