[NIPBL gene mutations in two children with Cornelia de Lange syndrome]

Area of Science:

• Genetics
• Rare Diseases
• Pediatrics

Background:

• Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by distinctive facial features, growth retardation, and developmental abnormalities.
• Mutations in several genes, including NIPBL, SMC1A, SMC3, HDAC8, RAD21, EP300, and ANKRD11, are known to cause CdLS.

Observation:

• Two unrelated children, a boy and a girl, presented in infancy with growth retardation and characteristic facial dysmorphia suggestive of CdLS.
• Patient 1 exhibited congenital heart defects and unique dermatoglyphics, while Patient 2 had a cleft palate and hearing impairment.
• Clinical manifestations in both children strongly indicated Cornelia de Lange syndrome.

Findings:

• High-throughput and Sanger sequencing identified novel mutations in the NIPBL gene in both patients.
• One patient harbored a frameshift mutation (c.7834dupA) in NIPBL, leading to a truncated protein (p.R2612fsX20).
• The other patient carried a nonsense mutation (c.505C>T) in NIPBL, resulting in a premature stop codon and a truncated protein (Q169X).

Implications:

• These findings expand the spectrum of known NIPBL mutations associated with Cornelia de Lange syndrome.
• Identification of novel mutations aids in understanding the genotype-phenotype correlations in CdLS.
• Genetic diagnosis is crucial for accurate prognosis and genetic counseling in families affected by CdLS.