Pure familial 6q21q22.1 duplication in two generations

Area of Science:

• Genetics
• Human Molecular Genetics
• Cytogenetics

Background:

• Familial transmission of unbalanced chromosomal abnormalities is infrequently documented.
• Partial duplications of chromosome segments can lead to complex genetic disorders.
• Understanding inheritance patterns of chromosomal abnormalities is crucial for genetic counseling.

Observation:

• A case of maternal inheritance of a pure partial duplication of chromosome 6 long arm (dup(6)(q21q22.1)) is presented.
• The proband exhibited intrauterine growth retardation (IUGR), moderate intellectual disability, and facial dysmorphism.
• Molecular cytogenetics confirmed a 5-10 Mb duplication between 6q21 and 6q22.1.

Findings:

• The proband's mother shared the same chromosomal abnormality and a similar, though less severe, phenotype.
• Variability in clinical presentation between generations suggests factors like imprinting, mosaicism, or age-related attenuation.
• This case, along with three previously reported instances, aids in refining karyotype-phenotype correlations for 6q21q22 duplications.

Implications:

• This report expands the understanding of rare chromosomal disorders and their inheritance.
• Refined karyotype-phenotype correlations improve diagnostic accuracy and genetic counseling for 6q duplications.
• Further research into the mechanisms causing phenotypic variability in inherited chromosomal abnormalities is warranted.