<unk>  has an autosomal recessive pattern of inheritance.<unk>  syndrome, as with the other disorders within the 3MC syndrome consideration, is caused by mutations in the COLLEC11 and MASP1 genes. In an investigation by Rooryck et al. (2011), eleven families affected by 3MC syndrome were studied, which resulted in the identification of these two mutations. Both genes encode proteins of the lectin complement pathway, which plays a role in the complement system of innate, or non-specific immunity in humans and other species. The COLLEC11, or CL-K1 gene is located on the short arm of chromosome 2 (2p25.3) in humans. The CL-K1 protein is a C-type lectin, and belongs to the collectin family of these proteins. Other than its role in innate immunity, the protein is thought to be involved in the development of tissues including craniofacial cartilage, the heart and kidney during embryogenesis. This function in<unk>  development was corroborated through study of the zebrafish, where mutations in its version of CL-K1 contributed to craniofacial abnormalities (such as Craniofacial clefts) possibly associated with errors in neural crest cell migration. The short and long arm of a typical human chromosome. The MASP1, or Mannan-binding Serine Protease I gene is located on the long arm of human chromosome 3 at 3q27-q28. The protein is a type of connectin called a mannan-binding lectin, which plays a role in innate immunity by binding to pathogens such as viruses including HIV. As described by Sirmaci et al. (2010), three Turkish individuals from two consanguineous families (the children of relatives such as cousins are said to be in a consanguineous family) with various characteristics of 3MC syndrome, including<unk>  dysmorphism and a caudal appendage, were evaluated. Investigation of homologous chromosomes through gene mapping revealed an autozygous region (a location on a chromosome where both alleles of a gene originate from a common ancestor) at chromosome 3q27 in both families. In one family, a missense mutation in MASP1 at this location resulted in the replacement of the amino acid glycine by arginine at position 687 in the gene sequence. The mutation cosegregated with the observed phenotype. In individuals from the second family, DNA sequencing of MASP1 showed a nonsense mutation that resulted in a deactivation of tryptophan at position 290 in the gene, that also cosegregated with the phenotype. Both mutations occur in a form of MASP1 known to process IGFBP5; loss of this function associated with mutation of MASP1 causes disruptions in the availability of insulin-like growth factor during craniofacial and musculoskeletal development during the embryonic period. These results indicate that mutations in MASP1 are responsible for an array of features found with malformation disorders including<unk>  syndrome. The syndrome is inherited in an autosomal recessive manner. This means the defective gene(s) responsible for the disorder (COLLEC11, MASP1) is located on an autosome (chromosomes 2 and 3 are autosomes), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
Malpuech facial clefting syndrome
Nager acrofacial dysostosis
Branchio-oculo-facial syndrome
Otofacial syndrome
Liber pantegni
Cleft Lip and Palate Association
Ablepharon macrostomia syndrome
Urofacial syndrome