Whole exome sequencing identifies novel pathogenic variants in TGM1 and ALOX12B in patients with hereditary ichthyosis.
ALOX12B
Exome sequencing
Hereditary Ichthyosis
TGM1
Journal
Archives of dermatological research
ISSN: 1432-069X
Titre abrégé: Arch Dermatol Res
Pays: Germany
ID NLM: 8000462
Informations de publication
Date de publication:
07 Dec 2023
07 Dec 2023
Historique:
received:
03
07
2023
accepted:
09
11
2023
revised:
25
10
2023
medline:
11
12
2023
pubmed:
7
12
2023
entrez:
7
12
2023
Statut:
epublish
Résumé
Hereditary ichthyosis is a clinically and genetically heterogeneous disorder associated with more than 50 genes with TGM1, ALOX12B, and ALOXE3 being the most prevalent. Establishing an accurate diagnosis is important for effective genetic counseling and optimal patient management. We studied the diagnostic value of whole exome sequencing (WES) in a small case series with hereditary ichthyosis. During a 1-year period, index cases of 5 unrelated families clinically diagnosed with hereditary ichthyosis went through WES, followed by extensive segregation analysis. Prenatal diagnosis (PND) was conducted where indicated. We identified 4 homozygous variants-2 in TGM1 (c.655A > G and c.797A > G) and 2 in ALOX12B (c.527 + 2 T > G and c.1654G > T)-alongside a heterozygous variant in TGM1 (c.428G > A) in 5 families. The variants were all pathogenic/likely pathogenic according to the ACMG classification and segregation analysis, except for c.797A > G in TGM1 which remained a variant of unknown clinical significance. Four variants were novel. All families were referred either during pregnancy or before reproductive planning; 4 benefited from WES as it identified the mutation in the probands and enabled carrier detection in at-risk relatives; PND was conducted in 2 families. Our findings further support WES is a powerful tool for the comprehensive, accurate, and rapid molecular diagnosis of hereditary ichthyosis and can offer opportunities for reproductive planning, carrier screening and prenatal diagnosis to at-risk families.
Sections du résumé
BACKGROUND
BACKGROUND
Hereditary ichthyosis is a clinically and genetically heterogeneous disorder associated with more than 50 genes with TGM1, ALOX12B, and ALOXE3 being the most prevalent. Establishing an accurate diagnosis is important for effective genetic counseling and optimal patient management.
OBJECTIVE
OBJECTIVE
We studied the diagnostic value of whole exome sequencing (WES) in a small case series with hereditary ichthyosis.
METHODS
METHODS
During a 1-year period, index cases of 5 unrelated families clinically diagnosed with hereditary ichthyosis went through WES, followed by extensive segregation analysis. Prenatal diagnosis (PND) was conducted where indicated.
RESULTS
RESULTS
We identified 4 homozygous variants-2 in TGM1 (c.655A > G and c.797A > G) and 2 in ALOX12B (c.527 + 2 T > G and c.1654G > T)-alongside a heterozygous variant in TGM1 (c.428G > A) in 5 families. The variants were all pathogenic/likely pathogenic according to the ACMG classification and segregation analysis, except for c.797A > G in TGM1 which remained a variant of unknown clinical significance. Four variants were novel. All families were referred either during pregnancy or before reproductive planning; 4 benefited from WES as it identified the mutation in the probands and enabled carrier detection in at-risk relatives; PND was conducted in 2 families.
CONCLUSION
CONCLUSIONS
Our findings further support WES is a powerful tool for the comprehensive, accurate, and rapid molecular diagnosis of hereditary ichthyosis and can offer opportunities for reproductive planning, carrier screening and prenatal diagnosis to at-risk families.
Identifiants
pubmed: 38060040
doi: 10.1007/s00403-023-02775-3
pii: 10.1007/s00403-023-02775-3
doi:
Substances chimiques
ALOX12B protein, human
EC 1.13.11.31
Arachidonate 12-Lipoxygenase
EC 1.13.11.31
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
24Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Références
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