Newborns main panel

Gene: SLC16A2

The mechanism of pathogenicity is loss-of-function (LOF).

Created: 1 Jun 2023, 2:40 p.m. | Last Modified: 1 Jun 2023, 2:40 p.m.

Panel Version: 0.137

SLC16A2 curation results (clinicalgenome.org)

Created: 1 Jun 2023, 12:22 p.m. | Last Modified: 1 Jun 2023, 12:22 p.m.

Panel Version: 0.135

MOI reviewed by clinical team. Mafalda Gomes comment: Most heterozygous females are not clinically affected but may have minor thyroid test abnormalities. Heterozygous females are generally asymptomatic and have no specific phenotypic findings. About 25% of heterozygous female have an abnormal thyroid profile with elevated T3 levels without any neurologic manifestations [Ramos et al 2011, Garca-de Teresa et al 2015]. Developmental delay and intellectual disability have been reported in heterozygous females in rare instances, perhaps due to skewed X-chromosome inactivation [Dumitrescu et al 2004, Schwartz et al 2005, Herzovich et al 2007, Garca-de Teresa et al 2015]. One female had typical features of AHDS with a de novo translocation disrupting SLC16A2 and unfavorable nonrandom X-chromosome inactivation [Frints et al 2008]. One exception of note was the finding in one female of a whole or partial deletion of one X chromosome and a SLC16A2 pathogenic variant on the other X chromosome. However, whether a causative relationship exists between SLC16A2 pathogenic variants and cognitive impairments in heterozygous females has yet to be proven [Schwartz et al 2005].

Created: 10 Mar 2023, 10:37 a.m. | Last Modified: 10 Mar 2023, 10:37 a.m.

Panel Version: 0.40

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

Phenotypes
Allan-Herndon-Dudley syndrome