Review of clinical and molecular variability in autosomal recessive cutis laxa 2A

doi:10.1002/ajmg.a.62047

Review

. 2021 Mar;185(3):955-965.

doi: 10.1002/ajmg.a.62047. Epub 2020 Dec 27.

Review of clinical and molecular variability in autosomal recessive cutis laxa 2A

Silvia Morlino¹, Grazia Nardella¹, Stefano Castellana², Lucia Micale¹, Massimiliano Copetti³, Carmela Fusco¹, Marco Castori¹

Affiliations

¹ Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy.
² Unit of Bioinformatics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy.
³ Unit of Biostatistics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy.

PMID: 33369135
DOI: 10.1002/ajmg.a.62047

Review

Review of clinical and molecular variability in autosomal recessive cutis laxa 2A

Silvia Morlino et al. Am J Med Genet A. 2021 Mar.

. 2021 Mar;185(3):955-965.

doi: 10.1002/ajmg.a.62047. Epub 2020 Dec 27.

Authors

Silvia Morlino¹, Grazia Nardella¹, Stefano Castellana², Lucia Micale¹, Massimiliano Copetti³, Carmela Fusco¹, Marco Castori¹

Affiliations

¹ Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy.
² Unit of Bioinformatics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy.
³ Unit of Biostatistics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy.

PMID: 33369135
DOI: 10.1002/ajmg.a.62047

Abstract

ATP6V0A2-related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A), is a subtype of hereditary cutis laxa originally characterized by skin, skeletal, and neurological involvement, and a combined defect of N-glycosylation and O-glycosylation. The associated clinical spectrum subsequently expanded to a less severe phenotype dominated by cutaneous involvement. At the moment, ARCL2A was described in a few case reports and series only. An Italian adult woman ARCL2A with a phenotype restricted to skin and the two novel c.3G>C and c.1101dup ATP6V0A2 variants has been reported. A systematic literature review allowed us to identify 69 additional individuals from 64 families. Available data were scrutinized in order to describe the clinical and molecular variability of ARCL2A. About 78.3% of known variants were predicted null alleles, while 11 were missense and 2 affected noncanonical splice sites. Age at ascertainment appeared as the unique phenotypic discriminator with earlier age more commonly associated with facial dysmorphism (p .02), high/cleft palate (p .005), intellectual disability/global developmental delay (p .013), and seizures (p .024). No specific genotype-phenotype correlations were identified. This work confirmed the existence of an attenuated phenotype associated with ATP6V0A2 biallelic variants and offers an updated critique to the clinical and molecular variability of ARCL2A.

Keywords: ARCL2A; ATP6V0A2; cutis laxa; genotype-phenotype correlations; mutation repertoire.

PubMed Disclaimer

Cited by

Identification of a novel intronic variant of ATP6V0A2 in a Han-Chinese family with cutis laxa.
Zhang Y, Sun M, Li N, Zhao Y, Zhang F, Shu J, Liu Y, Cai C. Zhang Y, et al. Mol Biol Rep. 2024 Apr 10;51(1):498. doi: 10.1007/s11033-024-09446-0. Mol Biol Rep. 2024. PMID: 38598037

References

REFERENCES

1. Bahena-Bahena, D., Lopez-Valdez, J., Raymond, K., Salinas-Marin, R., Ortega-Garcia, A., Ng, B. G., … Martinez-Duncker, I. (2014). ATP6V0A2 mutations present in two Mexican mestizo children with an autosomal recessive cutis laxa syndrome type IIA. Molecular Genetics and Metabolism Reports, 1, 203-212. https://doi.org/10.1016/j.ymgmr.2014.04.003
1. Basel-Vanagaite, L., Sarig, O., Hershkovitz, D., Fuchs-Telem, D., Rapaport, D., Gat, A., … Sprecher, E. (2009). RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome. American Journal of Human Genetics, 85, 254-263. https://doi.org/10.1016/j.ajhg.2009.07.001
1. Baumgartner, M. R., Hu, C. A., Almashanu, S., Steel, G., Obie, C., Aral, B., … Valle, D. (2000). Hyperammonemia with reduced ornithine, citrulline, arginine and proline: A new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. Human Molecular Genetics, 9, 2853-2858. https://doi.org/10.1093/hmg/9.19.2853
1. Beyens, A., Moreno-Artero, E., Bodemer, C., Cox, H., Gezdirici, A., Yilmaz Gulec, E., … Callewaert, B. (2019). ATP6V0A2-related cutis laxa in 10 novel patients: Focus on clinical variability and expansion of the phenotype. Experimental Dermatology, 28, 1142-1145. https://doi.org/10.1111/exd.13723
1. Fischer, B., Dimopoulou, A., Egerer, J., Gardeitchik, T., Kidd, A., Jost, D., … Kornak, U. (2012). Further characterization of ATP6V0A2-related autosomal recessive cutis laxa. Human Genetics, 131, 1761-1773. https://doi.org/10.1007/s00439-012-1197-8

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Supplementary concepts

Actions

LinkOut - more resources

Full Text Sources
- Ovid Technologies, Inc.
- Wiley

[1] Bahena-Bahena, D., Lopez-Valdez, J., Raymond, K., Salinas-Marin, R., Ortega-Garcia, A., Ng, B. G., … Martinez-Duncker, I. (2014). ATP6V0A2 mutations present in two Mexican mestizo children with an autosomal recessive cutis laxa syndrome type IIA. Molecular Genetics and Metabolism Reports, 1, 203-212. https://doi.org/10.1016/j.ymgmr.2014.04.003

[2] Bahena-Bahena, D., Lopez-Valdez, J., Raymond, K., Salinas-Marin, R., Ortega-Garcia, A., Ng, B. G., … Martinez-Duncker, I. (2014). ATP6V0A2 mutations present in two Mexican mestizo children with an autosomal recessive cutis laxa syndrome type IIA. Molecular Genetics and Metabolism Reports, 1, 203-212. https://doi.org/10.1016/j.ymgmr.2014.04.003

[3] Basel-Vanagaite, L., Sarig, O., Hershkovitz, D., Fuchs-Telem, D., Rapaport, D., Gat, A., … Sprecher, E. (2009). RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome. American Journal of Human Genetics, 85, 254-263. https://doi.org/10.1016/j.ajhg.2009.07.001

[4] Basel-Vanagaite, L., Sarig, O., Hershkovitz, D., Fuchs-Telem, D., Rapaport, D., Gat, A., … Sprecher, E. (2009). RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome. American Journal of Human Genetics, 85, 254-263. https://doi.org/10.1016/j.ajhg.2009.07.001

[5] Baumgartner, M. R., Hu, C. A., Almashanu, S., Steel, G., Obie, C., Aral, B., … Valle, D. (2000). Hyperammonemia with reduced ornithine, citrulline, arginine and proline: A new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. Human Molecular Genetics, 9, 2853-2858. https://doi.org/10.1093/hmg/9.19.2853

[6] Baumgartner, M. R., Hu, C. A., Almashanu, S., Steel, G., Obie, C., Aral, B., … Valle, D. (2000). Hyperammonemia with reduced ornithine, citrulline, arginine and proline: A new inborn error caused by a mutation in the gene encoding delta(1)-pyrroline-5-carboxylate synthase. Human Molecular Genetics, 9, 2853-2858. https://doi.org/10.1093/hmg/9.19.2853

[7] Beyens, A., Moreno-Artero, E., Bodemer, C., Cox, H., Gezdirici, A., Yilmaz Gulec, E., … Callewaert, B. (2019). ATP6V0A2-related cutis laxa in 10 novel patients: Focus on clinical variability and expansion of the phenotype. Experimental Dermatology, 28, 1142-1145. https://doi.org/10.1111/exd.13723

[8] Beyens, A., Moreno-Artero, E., Bodemer, C., Cox, H., Gezdirici, A., Yilmaz Gulec, E., … Callewaert, B. (2019). ATP6V0A2-related cutis laxa in 10 novel patients: Focus on clinical variability and expansion of the phenotype. Experimental Dermatology, 28, 1142-1145. https://doi.org/10.1111/exd.13723

[9] Fischer, B., Dimopoulou, A., Egerer, J., Gardeitchik, T., Kidd, A., Jost, D., … Kornak, U. (2012). Further characterization of ATP6V0A2-related autosomal recessive cutis laxa. Human Genetics, 131, 1761-1773. https://doi.org/10.1007/s00439-012-1197-8

[10] Fischer, B., Dimopoulou, A., Egerer, J., Gardeitchik, T., Kidd, A., Jost, D., … Kornak, U. (2012). Further characterization of ATP6V0A2-related autosomal recessive cutis laxa. Human Genetics, 131, 1761-1773. https://doi.org/10.1007/s00439-012-1197-8

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Review of clinical and molecular variability in autosomal recessive cutis laxa 2A

Affiliations

Review of clinical and molecular variability in autosomal recessive cutis laxa 2A

Authors

Affiliations

Abstract

Similar articles

Cited by

References

REFERENCES

Publication types

MeSH terms

Substances

Supplementary concepts

LinkOut - more resources

Full Text Sources

Abstract

Similar articles

Cited by

References

REFERENCES

Publication types

MeSH terms

Substances

Supplementary concepts

Related information

LinkOut - more resources

Full Text Sources