Prepair 1000+

Gene: POLA1

Green List (high evidence)

Pigmentary disorder, reticulate, with systemic manifestations, X-linked MIM#301220 has only been reported in families with an intronic variant introducing a new exon (NM_001330360.2:c.1393-354A>G, MANE transcript). According to OMIM, the onset is in early childhood. Female carriers may have no manifestations or only skin pigmentation changes. However, males may die early from systemic disease.

Van Esch-O'Driscoll syndrome MIM#301030 is a rare cause of syndromic X-linked intellectual disability characterised by short stature, microcephaly, variable degree of intellectual disability, and hypogonadotropic hypogonadism. It has been reported in at least 5 families (PMID: 31006512). According to OMIM, carrier females are unaffected.

The recurrent intronic variant (chrX:24726579 GRCh38 or chrX:24744696 GRCh37) is well covered by the current WES in use for Prepair. In addition, both conditions have enough evidence for gene-disease association. Therefore, this gene can be made green now.

Created: 21 Jan 2025, 4:03 a.m. | Last Modified: 21 Jan 2025, 4:03 a.m.

Panel Version: 1.1257

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

Phenotypes
Pigmentary disorder, reticulate, with systemic manifestations, X-linked MIM#301220; Van Esch-O'Driscoll syndrome MIM#301030

Publications

• 27019227
• 31006512