Ectodermal Dysplasia via the NECTIN1 Gene

Ectodermal dysplasia (ED) is a clinically and genetically heterogeneous disorder characterized by abnormal development of hair, teeth, nail or sweat glands (Visinoni et al. 2009). ED can be clinically divided into more than 150 subtypes.

Pathogenic variants in the NECTIN1 gene (also known as PVRL1) cause autosomal recessive cleft lip/palate-ectodermal dysplasia (CLPED1, also known as Zlotogora-Ogur syndrome and Margarita Island ectodermal dysplasia), autosomal recessive Orofacial cleft 7, as well as non-syndromic cleft of the lip/palate. NECTIN1 protein coded by NECTIN1 is a member of the immunoglobin (Ig) superfamily and plays a role in cell–cell adhesion. To date, more than 10 unique pathogenic variants have been reported. They include: missense (7), nonsense (2), small del/dup (3) and splicing (1). No large deletions/duplications have been reported (Sözen et al. 2001; Sözen et al. 2009; Avila et al. 2006, Human Gene Mutation Database). The 554G>A, p.Trp185* variant is commonly found in non-syndromic sporadic clefting cases in Northern Venezuela, with a carrier frequency of 1in 26 in the native population in that particular region (Sözen et al. 2001). In addition, heterozygous carriers of the 554G>A, p.Trp185* variant often have a broad and flat upper lip (Avila et al. 2006).

Due to limited publications, clinical sensitivity is currently unknown. Analytical sensitivity may be high as all the reported pathogenic variants are detectable by sequencing.

This test provides full coverage of all coding exons of the NECTIN1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).