Cutis Laxa NGS panel

Genes
(full coding
region):
ALDH18A1, ATP6V0A2, ATP7A, EFEMP2, ELN, FBLN5, GORAB, LTBP4, PYCR1, RIN2

List of diseases covered by the panel


Lab method: NGS panel
NGS panel with CNV

TAT: 6-9 weeks

Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.


Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of CL subtypes and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counselling

Cutis laxa (CL) is a group of rare connective tissue disorders affecting the elastic fibers of the skin and characterized by loss of elasticity resulting in loosening, and wrinkling of the skin. Both congenital or acquired forms exist.

In inherited CL, an abnormal synthesis of extracellular matrix proteins occurs due to defects in genes coding for diverse extracellular matrix components. Besides skin anomalies, in most CL forms multiple organs are involved, leading to severe and in some forms even lethal multisystem disorders involving skeletal, cardiovascular, pulmonary, and central nervous systems. Different inborn errors of metabolism have been described with variable severity. Although the increasing number of CL-related diseases are described, a large part of the cases remain genetically unsolved.

The specific symptoms, severity and prognosis can vary greatly depending upon the specific type of CL and the presence and extent of associated symptoms. The considerable variability can occur even among individuals with the same subtype and even among members of the same family. In general, the autosomal recessive forms of CL tend to be more severe than the autosomal dominant forms.

The cutis laxa panel covers the most of known genes related to inherited forms of CL subtypes and a range of disorders with CL symptoms. Currently, not all of the causative genes have been identified yet.

CL can be inherited in an autosomal dominant or autosomal recessive inheritance pattern.

CL affects males and females equally and individuals of all ethnic groups. The disorder has been reported in approximately 400 families worldwide. CL is estimated to affect 1 in 1,000,000 individuals in the general population. The adequate frequency of CL is difficult to estimate due to misdiagnosed or undiagnosed individuals.

References:
Callewaert BL, Urban Z. LTBP4-Related Cutis Laxa. 2016 Feb 11. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK343782/
Kaler SG. ATP7A-Related Copper Transport Disorders. 2003 May 9 [Updated 2016 Aug 18]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1413/
Loeys B, De Paepe A, Urban Z. EFEMP2-Related Cutis Laxa. 2011 May 12 [Updated 2015 Jul 23]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Table 2. [Disorders to Consider in the Differential Diagnosis of Cutis Laxa]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK54467/table/efemp2-cutis-laxa.T.disorders_to_conside/
Mohamed M, Voet M, Gardeitchik T, Morava E. Cutis Laxa. Adv Exp Med Biol. 2014;802:161-184. doi:10.1007/978-94-007-7893-1_11. PMID: 24443027
Mohamed M, Kouwenberg D, Gardeitchik T, Kornak U, Wevers RA, Morava E. Metabolic cutis laxa syndromes. J Inherit Metab Dis. 2011;34(4):907-916. doi:10.1007/s10545-011-9305-9. PMID: 21431621
Ritelli M, Cammarata‐ Scalisi F, Cinquina V, Colombi M. Clinical and molecular characterization of an 18‐month‐old infant with autosomal recessive cutis laxa type 1C due to a novel LTBP4 pathogenic variant, and literature review. Mol Genet Genomic Med . 2019;7:e735. https ://doi.org/10.1002/mgg3.735. PMID: 31115174
Van Maldergem L, Dobyns W, Kornak U. ATP6V0A2-Related Cutis Laxa. 2009 Mar 19 [Updated 2015 Feb 12]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5200/
Van Maldergem L, Loeys B. FBLN5-Related Cutis Laxa. 2009 Mar 19 [Updated 2018 Aug 16]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5201/