Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
Images in Dermatology
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Media and news
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
Generic selectors
Exact matches only
Search in title
Search in content
Post Type Selectors
Search in posts
Search in pages
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
Images in Dermatology
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Media and news
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Images
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Reviewers 2022
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Snippets
Special Article
Specialty Interface
Studies
Study Letter
Study Letters
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Review and Meta-Analysis
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guideline-IADVL
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
Therapy Letters
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Letter to the Editor - Observation Letter
2020:86:5;555-559
doi: 10.4103/ijdvl.IJDVL_947_19
PMID: 32719197

A novel mutation in LAMA3A gene in a child with laryngo-onycho-cutaneous syndrome from the Indian subcontinent

PSS Ranugha, Veeranna Shastry
 Department of Dermatology, JSS Medical College and Hospital, JSSAHER, Mysore, Karnataka, India

Correspondence Address:
PSS Ranugha
Department of Dermatology, JSS Medical College and Hospital, JSSAHER, Mysore, Karnataka
India
Published: 22-Jul-2020
How to cite this article:
Ranugha P, Shastry V. A novel mutation in LAMA3A gene in a child with laryngo-onycho-cutaneous syndrome from the Indian subcontinent. Indian J Dermatol Venereol Leprol 2020;86:555-559
Copyright: (C)2020 Indian Journal of Dermatology, Venereology, and Leprology

Sir,

Laryngo-onycho-cutaneous or Shabbir syndrome (OMIM 245660) is a rare autosomal recessive epithelial disorder confined to the Punjabi Muslim population.[1] Herein, we present a child with laryngo-onycho-cutaneous syndrome demonstrating a new mutation in LAMA3A gene.

A 2-year-old Bangladeshi girl, born out of non-consanguineous parentage, presented with a history of hoarse cry since birth and spontaneous blistering, automatic reddish growths from eyelids, wounds on the body and discoloration of nails since 6 months of age. On examination, we noted superficial erosions and ulcers with exuberant granulation tissue (ranging in size from 7× 4 to 15× 4 cm) on the right cheek, upper chest and left shoulder [Figure - 1]a. Multiple hyperpigmented to violaceous papules and plaques with central erosions and crusting were noted on the trunk and limbs [Figure - 1]b. We also observed fleshy growths from both upper eyelids without any bleeding, discharge or matting. Brownish discoloration of teeth was observed along with few dystrophic nails [Figure - 1]c and [Figure - 1]d. Ear, nose and throat referral was made and laryngoscopy revealed multiple tense bullae in the larynx [Figure - 1]e. There was no history of breathing difficulty. Parents denied any history of recurrent skin or respiratory infections or similar complaints in any family member. Developmental milestones were adequate for her age. Routine blood investigations and serum immunoglobulin levels were normal. Absence of hair or sweating abnormalities, icthyosis, palmoplantar keratoderma, photosensitivity and acantholysis on skin histopathology ruled out ectodermal dysplasias and other genodermatoses associated with blistering. Ultrasonogram of the abdomen revealed a fatty liver with borderline splenomegaly.

We identified three different mutations in different exons of the LAMA3A gene on chromosome 18 by molecular analysis of the child's blood sample. A heterozygous two base pair deletion in exon 47 of the LAMA3 gene resulted in a frame shift and premature truncation of the protein, 5 amino acids downstream to codon 1967 (p. Ser1967GlnfsTer5; ENST00000313654) was detected [Figure - 2]. A heterozygous missense mutation was detected in exon 13 of the LAMA3 gene (chr18:21390398C>T; depth: 164×), which led to substitution of amino acid tryptophan for arginine at codon 558 (p. Arg558Trp; ENST00000313654). This observed variation lies in the lamin in epidermal growth factor domain of the LAMA3 protein. Another heterozygous missense variation in exon 28 of the LAMA3 gene (chr18:21422480G>A; depth: 74×) was found which resulted in amino acid substitution of glutamine for arginine at codon 1153 (p. Arg1153Gln; ENST00000313654).

Figure 2: Sequence chromatogram and alignment to the reference sequence showing the variation in exon 47 of the LAMA3 gene (chr18:21479311_21479312delTT; c.5898_5899delTT; p. Ser1967GlnfsTer5) detected in heterozygous condition

Based on clinical findings and mutations in the LAMA3A gene, we made a diagnosis of laryngo-onycho-cutaneous syndrome. We advised daily dressing of the wounds, topical steroids and antihistamines. Parents were taught about wound care and ophthalmologic intervention was sought for excision of conjunctival granulation tissue and amniotic membrane transplant. The child expired after 6 months following respiratory distress.

Laryngo-onycho-cutaneous syndrome is a localized variant of junctional epidermolysis bullosa. It starts in infancy with chronic erosions affecting the face (predominantly perinasal and perioral). The nails are involved with marked periungual and subungual inflammation. Hoarseness is a universal feature characterized by altered cry at birth. The teeth may be notched. Exuberant skin and mucosal granulation tissue formation can impair wound healing and result in laryngeal obstruction and blindness.[2] Although these findings are common to all types of junctional epidermolysis bullosa, the erosions and bullae are much extensive in generalized junctional epidermolysis bullosa whereas minimal blistering with excessive granulation tissue formation is characteristic of laryngo-onycho-cutaneous syndrome. Conjunctival eye lesions, characteristic of laryngo-onycho-cutaneous syndrome, are rare in other subtypes of junctional epidermolysis bullosa.[1]

The laminins are a family of heterotrimeric molecules, responsible for structural and functional integrity of basement membrane. Through the study of blistering skin diseases, it is now well-established that the a3 subunit of laminins-332, -321 and -311 plays an important role in mediating epidermal-dermal integrity and is essential for the skin to withstand mechanical stress.[3] Most mutations in both Herlitz and non-Herlitz forms of junctional epidermolysis bullosa disease are restricted to three genes, LAMA3, LAMB3 and LAMC2, that encode the α, β and γ subunits of laminin 332, respectively.[4]

The human LAMA3 gene encodes 76 exons from 318 kb of genomic DNA at chromosomal location 18q11.2 and has two transcripts LAMA3A and LAMA3B (B1 and B2).[3]In most laryngo-onycho-cutaneous cases of Punjabi origin, a homozygous recessive mutation has been detected in exon 39 of LAMA3A which encodes laminin 3A leading to the fore-shortening of a critical portion of the N terminus of the a3 chain of laminin-5 trimer.[3] Studies suggest altered homeostasis of extracellular matrix due to secretion of abbreviated a3 chain by the basal keratinocytes.[5],[6]

In our patient, we detected a novel heterozygous 2-base pair deletion in exon 47, not reported till date, leading to premature truncation of protein, which could be the possible pathogenic mutation. Absence of the N-terminal region of laminin alpha 3a in laryngo-onchyo-cutaneous syndrome results in excessive granulation tissue production at wound sites.[5]

We also found heterozygous missense mutations in exon 13 and exon 28, however, further studies are needed to highlight its significance. The different mutations reported in laryngo-onycho-cutaneous syndrome till date are described in [Table - 1].[5],[6],[7]

Table 1: Reports of mutations in laryngo-onycho-cutaneous syndrome

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal the identity but anonymity cannot be guaranteed.

Acknowledgments

We would like to thank Dr. Ravi N. Hiremagalore for helping us with the evaluation of the case.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References
1.
Cohn HI, Murrell DF. Laryngo-onycho-cutaneous syndrome. Dermatol Clin 2010;28:89-92.
[Google Scholar]
2.
McGrath JA. Genetic blistering diseases. In: Chalmers R, Barker J, Griffiths C, Bleiker T, Creamer D, editors. ROOK's Textbook of Dermatology. 9th ed. West Sussex, UK: John Wiley and Sons, Ltd.; 2016. p. 71.14.
[Google Scholar]
3.
Hamill KJ, Paller AS, Jones JC. Adhesion and migration, the diverse functions of the laminin alpha3 subunit. Dermatol Clin 2010;28:79-87.
[Google Scholar]
4.
Varki R, Sadowski S, Pfendner E, Uitto J. Epidermolysis bullosa. I. Molecular genetics of the junctional and hemidesmosomal variants.J Med Genet 2006;43:641-52.
[Google Scholar]
5.
McLean WH, Irvine AD, Hamill KJ, Whittock NV, Coleman-Campbell CM, Mellerio JE, et al. An unusual N-terminal deletion of the laminin alpha3a isoform leads to the chronic granulation tissue disorder laryngo-onycho-cutaneous syndrome. Hum Mol Genet 2003;12:2395-409.
[Google Scholar]
6.
Figueira EC, Crotty A, Challinor CJ, Coroneo MT, Murrell DF. Granulation tissue in the eyelid margin and conjunctiva in junctional epidermolysis bullosa with features oflaryngo-onycho-cutaneous syndrome. Clin Exp Ophthalmol 2007;35:163-6.
[Google Scholar]
7.
Barzegar M, Mozafari N, Kariminejad A, Asadikani Z, Ozoemena L, McGrath JA. A new homozygous nonsense mutation in LAMA3A underlying laryngo-onycho-cutaneous syndrome. Br J Dermatol. 2013 Dec;169(6):1353-6.
[Google Scholar]

Fulltext Views
2,735

PDF downloads
1,287
Show Sections