Interstitial deletions of chromosome 6q: genotype-phenotype correlation utilizing array CGH

Area of Science:

• Genetics
• Human Molecular Genetics
• Chromosomal Abnormalities

Background:

• Interstitial deletions of chromosome 6 long arm (6q) are uncommon genetic variations.
• Phenotypic variability in 6q deletions is often attributed to the size and precise location of the deleted segment.

Observation:

• Three new patients with 6q interstitial deletions were characterized using array comparative genomic hybridization (array CGH).
• Molecular breakpoints determined by array CGH refined breakpoints from conventional karyotyping in two patients.
• Two patients had deletions of 6-8.8 Mb within 6q16.2-->q21; the third had an 11.3 Mb deletion spanning 6q15-->q21.

Findings:

• All patients exhibited developmental delay, craniofacial dysmorphia, and ocular functional disorders.
• A common deleted region (6q16.2-->q21) suggests the presence of genes critical for brain and craniofacial development.
• Central diabetes insipidus in one patient may be linked to a deletion at 6q15.
• Loss of paternal alleles in all cases supports a predominantly paternal origin for 6q deletions.

Implications:

• Array CGH offers superior resolution for defining 6q deletion breakpoints compared to conventional karyotyping.
• The 6q16.2-->q21 region is implicated in neurodevelopmental and craniofacial morphogenesis.
• Further investigation into specific genes within deleted regions is warranted to understand diverse clinical manifestations, including central diabetes insipidus.