Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate

Area of Science:

• Genetics
• Developmental Biology
• Human Genomics

Background:

• Cleft lip and/or palate (CL/P) are common congenital facial anomalies with complex genetic and environmental causes.
• While numerous genetic loci are associated with CL/P, most are in noncoding regions, with few identified etiological coding variants.

Purpose of the Study:

• To identify potential etiological coding variants within the GREM1 gene, a known susceptibility locus for CL/P.
• To investigate the role of GREM1 coding variants in the etiology of cleft lip and/or palate.

Main Methods:

• DNA sequencing of the GREM1 gene in 397 sub-Saharan African individuals with CL/P and 192 controls.
• Sanger sequencing was employed to analyze sequence data for novel variants.
• Comparison of identified variants against public databases and existing literature.

Main Results:

• Two novel GREM1 coding variants, p.Pro164Ser and p.Gly61Asp, were identified in individuals with CL/P.
• These variants were absent in the control group and not previously reported in major genetic databases.
• The p.Gly61Asp variant was found in a van der Woude syndrome case with an additional IRF6 variant.

Conclusions:

• The study found a low burden of etiological coding variants in GREM1.
• These findings support the hypothesis that variants in regulatory elements of GREM1 are more likely responsible for its association with CL/P.
• Further research into noncoding regulatory regions of GREM1 is warranted.