ClinGen Dosage Sensitivity Curation Page

OFD1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000023.10) (NC_000023.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
11179005 In a family with orofaciodigital syndrome type I (OFD1), Ferrante et al. (2001) describe a 19 basepair deletion in exon 3 of the OFD1 gene, leading to a frameshift. This mutation segregates with the disease in this family and is not found in 90 normal X chromosomes.
11179005 In sporadic cases of orofaciodigital syndrome type I (OFD1), Ferrante et al. (2001) describe one nonsense mutation in OFD1 (121 C to T transition that creates a termination codon in exon 3), and one frameshift mutation in OFD1 (a deletion of G at position 1757). These were both de novo mutations and not found in 90 normal X chromosomes.
11950863 In a family with a mother and 2 daughters affected with orofaciodigital syndrome type I (OFD1), Rakkolainen et al. (2002) describe a 2 basepair insertion in exon 16 of the OFD1 gene that creates a frameshift and a premature stop codon at amino acid 666. This mutation was not found in 50 control individuals.

Haploinsufficiency phenotype comments:

Mutations in OFD1 cause orofaciodigital syndrome type I (OFD1), characterized by malformations of the face, oral cavity, and digits. OFD1 is an X-linked dominant condition with lethality in males. The haploinsufficiency score is based on this phenotype. Mutations in the OFD1 gene also cause Simpson-Golabi-Behmel syndrome type 2 (GBS2; MIM#300209) and Joubert syndrome-10 (JBTS10; MIM#300804), both of which are X-linked recessive. See OMIM for more information.

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.