Prepair 1000+

Gene: OFD1

Green List (high evidence)

Orofaciodigital syndrome I (MIM#311200) is X-linked dominant and is associated with severe disease in heterozygous females and is lethal in hemizygous males, this condition is not of interest in a carrier screening context as heterozygous females are expected to be affected.

However Joubert syndrome and Simpson-Golabi-Behmel syndrome are x-linked recessive where heterozygous females are generally not affected/only mildly affected. Therefore these conditions are of interest in carrier screening.

There is also a retinitis pigmentosa phenotype in OMIM but it seems to have limited evidence currently and appears to be associated with a deep intronic variant causing cryptic exon inclusion (PMID: 22619378). This variant at chrX:13768358 is well covered in lumi sequencing but does not have great coverage in twist v2. This gene is green on the RP panel therefore this is likely of interest in a carrier screening context.

there is a genotype phenotype correlation with protein length reduction and severity. missense of N-terminal PTCs are associated with OFD1, while C-terminal PTCs are associated with SGBS and Joubert syndrome (PMID: 31373179, PMID: 23033313, PMID: 16783569, OMIM).

Created: 31 Oct 2024, 1:49 a.m. | Last Modified: 31 Oct 2024, 1:49 a.m.

Panel Version: 1.545

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Joubert syndrome 10 MIM#300804; Simpson-Golabi-Behmel syndrome, type 2 MIM#300209; Retinitis pigmentosa 23 MIM#300424

Publications

• 22619378
• 31373179
• 23033313
• 16783569