Genotype-phenotype correlation in 13q13.3-q21.3 deletion

Area of Science:

• Genetics
• Developmental Biology
• Clinical Genetics

Background:

• Interstitial deletions of chromosome 13q are associated with diverse phenotypes dependent on deletion size and location.
• Deletions specifically within the 13q13-q21 region are infrequent, necessitating further genotype-phenotype correlation studies.

Observation:

• Two independent cases with de novo 13q13-q21 deletions were analyzed using high-resolution array comparative genomic hybridization, conventional karyotyping, and molecular techniques.
• The first patient, a 3-year-old girl, presented with mental retardation, dysmorphy, and a 13q13.3q21.31 deletion. The second case involved a fetus with a de novo del(13)(q14q21.2) and increased nuchal translucency.

Findings:

• A shared 13q14q21 chromosomal segment correlated with specific dysmorphic features including macrocephaly, high forehead, hypertelorism, large nose, malformed ears, and retrognathia.
• Both patients exhibited overgrowth, with measurements up to the 95th percentile, a rare finding in 13q deletion cases.
• Haploinsufficiency of candidate genes (CKAP2, SUGT1, LECT1, DCLK1, SMAD9), crucial for cell division and bone development, is proposed as a mechanism for overgrowth.

Implications:

• This study refines genotype-phenotype correlations for rare 13q13-q21 deletions, identifying a critical region for specific dysmorphic features and overgrowth.
• The findings suggest that cytogenetic analysis should be considered in patients presenting with overgrowth, even without other typical syndromic features.
• Understanding the role of candidate gene haploinsufficiency provides insights into the molecular mechanisms underlying developmental abnormalities associated with chromosomal deletions.