Identification of a Novel 19-bp Deletion Mutation in LTBP4 Using Exome Sequencing in Two Siblings with Autosomal Recessive Cutis Laxa Type 1C

Gupta, Neerja; Langeh, Nitika; Sridharan, Aparajit; Kabra, Madhulika

doi:10.1055/s-0039-1698806

Cited by 3 publications

(3 citation statements)

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“…Only 21 other cases of LTBP4related cutis laxa have been described among 20 families (B. Callewaert et al, 2013;N. Gupta et al, 2020;Ritelli et al, 2019;Su et al, 2015;Urban et al, 2009;Q.…”

Section: Discussionmentioning

confidence: 99%

“…ARCL1C is a very rare disorder. Only 21 other cases of LTBP4 ‐related cutis laxa have been described among 20 families (B. Callewaert et al, 2013 ; N. Gupta et al, 2020 ; Ritelli et al, 2019 ; Su et al, 2015 ; Urban et al, 2009 ; Q. Zhang et al, 2020 ) (Table S1 , Figure S1 ). The case reported here presents the clinical and molecular characteristics of ARCL1C.…”

Section: Discussionmentioning

confidence: 99%

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First report of a short in‐frame biallelic deletion removing part of the EGF‐like domain calcium‐binding motif in LTBP4 and causing autosomal recessive cutis laxa type 1C

Ravel

Comel²,

Wandzel³

et al. 2022

American J of Med Genetics Pt A

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Cutis laxa (CL) is a rare connective tissue disorder characterized by wrinkled, abundant and sagging skin, sometimes associated with systemic impairment. Biallelic alterations in latent transforming growth factor beta-binding protein 4 gene (LTBP4) cause autosomal recessive type 1C cutis laxa (ARCL1C, MIM #613177). The present report describes the case of a 17-months-old girl with cutis laxa together with a literature review of previous ARCL1C cases. Based on proband main clinical signs (cutis laxa and pulmonary emphysema), clinical exome sequencing (CES) was performed and showed a new nine base-pairs homozygous in-frame deletion in LTBP4 gene. RT-PCR and cDNA Sanger sequencing were performed in order to clarify its impact on RNA. This report demonstrates that a genetic alteration in the EGF-like 14 domain calcium-binding motif of LTBP4 gene is likely responsible for cutis laxa in our patient.autosomal recessive cutis laxa type 1C (ARCL1C), calcium-binding epidermal growth factor-like domain, LTBP4, Urban-Rifkin-Davis syndrome (URDS) | INTRODUCTIONCutis laxa is a group of rare connective tissue disorders characterized by loose and wrinkled skin. It is associated with skeletal and developmental abnormalities and, in some cases, severe systemic impairments (Beyens et al., 2021).Connective tissue is a supporting tissue consisting of three components: (1) secretory cells synthetizing ground substance and specific proteins which give connective tissue its characteristics, (2) elastin made elastic fibers, responsible for the skin elastic properties, and collagen made reticular fibers contributing to small blood vessels and soft tissues support, and (3) ground substance.Cutis laxa is the Latin term for sagging or slackened, nonstretchable skin. This wrinkle-like skin can be particularly noticeable on the face, neck, armpits, and limbs. Cutis laxa may be inherited or acquired.Acquired forms most often occur in adulthood, their etiology including infections, drugs, or paraneoplasia (Lewis et al., 2004).Three major groups are individualized based on the inheritance mode: autosomal dominant, autosomal recessive, and X-linked recessive cutis laxa.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

First report of a short in‐frame biallelic deletion removing part of the EGF‐like domain calcium‐binding motif in LTBP4 and causing autosomal recessive cutis laxa type 1C

Ravel

Comel²,

Wandzel³

et al. 2022

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…[3,4] Since its first description in 2009, only 27 cases of URDS have been documented in the world literature. [4][5][6][7][8][9][10][11][12][13] (Table 1) URDS is caused by mutation of the gene for Latent Transforming Growth Factor-β Binding Protein-4 (LTBP4). [14] This syndrome is characterized by predominant involvement of pulmonary, gastrointestinal, genitourinary, musculoskeletal and dermal systems.…”

Section: Introductionmentioning

confidence: 99%

On the curious association of diaphragmatic hernia and Urban-Rifkin-Davis Syndrome (Autosomal Recessive Cutis Laxa-1C): A collective review of 16 cases

Raveenthiran,

Darun,

Pavithra

et al. 2024

J Neonatal Surg

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Background: Autosomal recessive cutis laxa type-1C is also known as Urban-Rifkin-Davis syndrome (URDS). It is known to affect cardiopulmonary, integumentary, gastrointestinal, musculoskeletal and genitourinary systems. However, its frequent association with congenital diaphragmatic hernia has not previously been highlighted. Case Presentation: A newborn male with cutis laxa presented with respiratory distress at birth. The cause of dyspnoea was perinatal strangulation of the stomach in hiatus hernia. After surgical repair of the hernia, his respiratory distress temporarily improved but kept recurring periodically by various mechanisms in sequence namely pulmonary hypertension, tracheomalacia, pulmonary emphysema and finally he succumbed to pneumothorax. Genetic analysis revealed his skin condition as autosomal recessive cutis laxa type-1C which is also known as URDS. Exome sequencing revealed a novel frameshift mutation c.426delC (p.Cys143Alafs*41) of the LTBP4 gene in the exon 5 of Chromosome 19. Conclusion: Out of the 28 cases of URDS reported in the world literature 57% had congenital diaphragmatic hernia (CDH) and 53% of them died during infancy. Such a high incidence of CDH is not observed in other subtypes of elastic disorders. Thus, congenital diaphragmatic defects appear to be a characteristic diagnostic feature of URDS in patients with cutis laxa.

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Two novel compound heterozygous variants of LTBP4 in a Chinese infant with cutis laxa type IC and a review of the related literature

et al. 2020

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Background Autosomal recessive cutis laxa type IC (ARCL IC, MIM: #613177) results from a mutation in the LTBP4 gene (MIM: #604710) on chromosome 19q13. Case presentation A 28-day-old Chinese infant with generalized cutis laxa accompanied by impaired pulmonary, gastrointestinal, genitourinary, retinal hemorrhage, abnormality of coagulation and hyperbilirubinemia was admitted to our hospital. To find out the possible causes of these symptoms, whole-exome sequencing was performed on the infant. Two novel pathogenic frame-shift variants [c.605_606delGT (p.Ser204fs * 8) and c.1719delC (p.Arg574fs * 199)] of the LTBP4 gene associated with ARCL IC were found which was later verified by Sanger sequencing. The pathogenicity of mutations was subsequently assessed by several software programs and databases. In addition, an analytical review on the clinical phenotypes of the disease previously reported in literature was performed. Conclusions This is the first report of a Chinese infant with ARCL IC in China due to novel pathogenic variations of LTBP4. Our study extends the cutis laxa type IC mutation spectrum as well as the phenotypes associated with the disease in different populations.

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Identification of a Novel 19-bp Deletion Mutation in LTBP4 Using Exome Sequencing in Two Siblings with Autosomal Recessive Cutis Laxa Type 1C

Cited by 3 publications

References 11 publications

First report of a short in‐frame biallelic deletion removing part of the EGF‐like domain calcium‐binding motif in LTBP4 and causing autosomal recessive cutis laxa type 1C

First report of a short in‐frame biallelic deletion removing part of the EGF‐like domain calcium‐binding motif in LTBP4 and causing autosomal recessive cutis laxa type 1C

On the curious association of diaphragmatic hernia and Urban-Rifkin-Davis Syndrome (Autosomal Recessive Cutis Laxa-1C): A collective review of 16 cases

Two novel compound heterozygous variants of LTBP4 in a Chinese infant with cutis laxa type IC and a review of the related literature

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