Background
Nonsyndromic cleft lip and/or palate is one of the most common human birth defects worldwide that affects the lip and/or palate. The incidence of clefts varies among populations through ethnic, race, or geographical differences. The focus on Malay nonsyndromic cleft lip and/or palate (NSCL/P) is because of a scarce report on genetic study in relation to this deformity in Malaysia. We are interested to discuss about the genes that are susceptible to cause orofacial cleft formation in the family.
Methods
Genome‐wide linkage analysis was carried out on eight large extended families of NSCL/P with the total of 91 individuals among Malay population using microarray platform. Based on linkage analyses findings, copy number variation (CNV) of
LPHN2
,
SATB2
,
PVRL3
,
COL21A1,
and
TOX3
were identified in four large extended families that showed linkage evidence using quantitative polymerase chain reaction (qPCR) as for a validation purpose. Copy number calculated (CNC) for each genes were determined with Applied Biosystems CopyCallerTM Software v2.0. Normal CNC of the target sequence expected was set at two.
Results
Genome‐wide linkage analysis had discovered several genes including
TOX3
and
COL21A1
in four different loci 4p15.2‐p16.1, 6p11.2‐p12.3, 14q13‐q21, and 16q12.1. There was significant decreased,
p
< 0.05 of
SATB2
,
COL21A1,
and
TOX3
copy number in extended families compared to the normal controls.
Conclusion
Novel linkage evidence and significant low copy number of
COL21A1
and
TOX3
in NSCLP family was confirmed. These genes increased the risks toward NSCLP formation in that family traits.