An updated mutation spectrum of the γ-secretase complex: Novel NCSTN gene mutation in an Indian family with hidradenitis suppurativa and acne conglobata
Background: Hidradenitis suppurativa (HS) is a complex, chronic inflammatory skin disorder whose pathophysiology is poorly understood. Genetic studies have shown that HS is predisposed by mutations in the γ-secretase gene, but only a proportion of familial and partial sporadic cases have been shown...
| Published in: | Indian Journal of Dermatology |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2023-01-01
|
| Subjects: | |
| Online Access: | http://www.e-ijd.org/article.asp?issn=0019-5154;year=2023;volume=68;issue=2;spage=141;epage=147;aulast=Ratnamala |
| _version_ | 1851951077170085888 |
|---|---|
| author | Uppala Ratnamala Nayan K Jain Devendrasinh D Jhala Pullabatla V S. Prasad Nazia Saiyed Sreelatha Nair Uppala Radhakrishna |
| author_facet | Uppala Ratnamala Nayan K Jain Devendrasinh D Jhala Pullabatla V S. Prasad Nazia Saiyed Sreelatha Nair Uppala Radhakrishna |
| author_sort | Uppala Ratnamala |
| collection | DOAJ |
| container_title | Indian Journal of Dermatology |
| description | Background: Hidradenitis suppurativa (HS) is a complex, chronic inflammatory skin disorder whose pathophysiology is poorly understood. Genetic studies have shown that HS is predisposed by mutations in the γ-secretase gene, but only a proportion of familial and partial sporadic cases have been shown to possess such mutations. HS has high genetic heterogeneity and is thought to be triggered by a combination of genetics and environmental factors. Aims: The study aimed to investigate the genetic causes of HS in a large cohort of patients and to update the mutation spectrum of γ-secretase complex genes. Methods: We conducted mutational screening of 95 sporadic HS cases and one large family with both HS and acne conglobata (AC) to identify mutations in the coding and splice junction region of γ-secretase complex genes (nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN), and aph-1 homolog B, gamma-secretase subunit (APH1B)). Results: Our study identified a nucleotide substitution of 1876C>T in the NCSTN gene, which caused a stop codon (p.Arg626X) in the affected members of a large family with HS and AC. No pathogenic variants were detected in 95 sporadic cases of HS, indicating there is possible genetic heterogeneity. Conclusion: We report a new family with a nonsense mutation in the NCSTN gene that supports the role of the γ-secretase complex genes in HS with AC. The updated γ-secretase mutation spectrum for HS now includes 78 mutations. |
| format | Article |
| id | doaj-art-a40394acccdd4f1eb331eb832e29ffe4 |
| institution | Directory of Open Access Journals |
| issn | 0019-5154 1998-3611 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| spelling | doaj-art-a40394acccdd4f1eb331eb832e29ffe42025-08-19T21:46:34ZengWolters Kluwer Medknow PublicationsIndian Journal of Dermatology0019-51541998-36112023-01-0168214114710.4103/ijd.ijd_995_21An updated mutation spectrum of the γ-secretase complex: Novel NCSTN gene mutation in an Indian family with hidradenitis suppurativa and acne conglobataUppala RatnamalaNayan K JainDevendrasinh D JhalaPullabatla V S. PrasadNazia SaiyedSreelatha NairUppala RadhakrishnaBackground: Hidradenitis suppurativa (HS) is a complex, chronic inflammatory skin disorder whose pathophysiology is poorly understood. Genetic studies have shown that HS is predisposed by mutations in the γ-secretase gene, but only a proportion of familial and partial sporadic cases have been shown to possess such mutations. HS has high genetic heterogeneity and is thought to be triggered by a combination of genetics and environmental factors. Aims: The study aimed to investigate the genetic causes of HS in a large cohort of patients and to update the mutation spectrum of γ-secretase complex genes. Methods: We conducted mutational screening of 95 sporadic HS cases and one large family with both HS and acne conglobata (AC) to identify mutations in the coding and splice junction region of γ-secretase complex genes (nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN), and aph-1 homolog B, gamma-secretase subunit (APH1B)). Results: Our study identified a nucleotide substitution of 1876C>T in the NCSTN gene, which caused a stop codon (p.Arg626X) in the affected members of a large family with HS and AC. No pathogenic variants were detected in 95 sporadic cases of HS, indicating there is possible genetic heterogeneity. Conclusion: We report a new family with a nonsense mutation in the NCSTN gene that supports the role of the γ-secretase complex genes in HS with AC. The updated γ-secretase mutation spectrum for HS now includes 78 mutations.http://www.e-ijd.org/article.asp?issn=0019-5154;year=2023;volume=68;issue=2;spage=141;epage=147;aulast=Ratnamalachronic skin disordersgenetic heterogeneityhidradenitis suppurativancstn gene mutation |
| spellingShingle | Uppala Ratnamala Nayan K Jain Devendrasinh D Jhala Pullabatla V S. Prasad Nazia Saiyed Sreelatha Nair Uppala Radhakrishna An updated mutation spectrum of the γ-secretase complex: Novel NCSTN gene mutation in an Indian family with hidradenitis suppurativa and acne conglobata chronic skin disorders genetic heterogeneity hidradenitis suppurativa ncstn gene mutation |
| title | An updated mutation spectrum of the γ-secretase complex: Novel NCSTN gene mutation in an Indian family with hidradenitis suppurativa and acne conglobata |
| title_full | An updated mutation spectrum of the γ-secretase complex: Novel NCSTN gene mutation in an Indian family with hidradenitis suppurativa and acne conglobata |
| title_fullStr | An updated mutation spectrum of the γ-secretase complex: Novel NCSTN gene mutation in an Indian family with hidradenitis suppurativa and acne conglobata |
| title_full_unstemmed | An updated mutation spectrum of the γ-secretase complex: Novel NCSTN gene mutation in an Indian family with hidradenitis suppurativa and acne conglobata |
| title_short | An updated mutation spectrum of the γ-secretase complex: Novel NCSTN gene mutation in an Indian family with hidradenitis suppurativa and acne conglobata |
| title_sort | updated mutation spectrum of the γ secretase complex novel ncstn gene mutation in an indian family with hidradenitis suppurativa and acne conglobata |
| topic | chronic skin disorders genetic heterogeneity hidradenitis suppurativa ncstn gene mutation |
| url | http://www.e-ijd.org/article.asp?issn=0019-5154;year=2023;volume=68;issue=2;spage=141;epage=147;aulast=Ratnamala |
| work_keys_str_mv | AT uppalaratnamala anupdatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT nayankjain anupdatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT devendrasinhdjhala anupdatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT pullabatlavsprasad anupdatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT naziasaiyed anupdatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT sreelathanair anupdatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT uppalaradhakrishna anupdatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT uppalaratnamala updatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT nayankjain updatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT devendrasinhdjhala updatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT pullabatlavsprasad updatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT naziasaiyed updatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT sreelathanair updatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata AT uppalaradhakrishna updatedmutationspectrumofthegsecretasecomplexnovelncstngenemutationinanindianfamilywithhidradenitissuppurativaandacneconglobata |