Novel mutation in <i>TP</i><i>63</i> associated with ectrodactyly ectodermal dysplasia and clefting syndrome and T cell lymphopenia

Giampietro, Philip F.; Baker, Mei W.; Basehore, Monica J.; Jones, Julie R.; Seroogy, Christine M.

doi:10.1002/ajmg.a.35885

Cited by 12 publications

(5 citation statements)

References 11 publications

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“…Failed TREC‐based newborn screening for SCID was found in individuals 1 and 2, and was previously reported for another child with TP63 pathogenic variant (Giampietro et al, ). Individuals 1 and 2, in addition to the previously reported individual, were shown not to have SCID with follow up testing, but were found to have T‐cell lymphopenia.…”

Section: Discussionsupporting

confidence: 68%

“…The majority of pathogenic variants are missense with occasional nonsense variants (Rinne, Bolat, Meijer, Scheffer & Bokhoven, ), small deletions (Giampietro, Baker, Basehore, Jones & Seroogy, ), splice site variants (Kantaputra, Matangkasombut & Sripathomsawat, ), and one large deletion (Aradhya et al, ). There is a large amount of intra‐ and inter‐familial phenotypic variability, but common findings across TP63 ‐related disorders include cleft lip and/or palate, ectodermal dysplasia, hand and/or foot abnormalities, skin pigmentary differences, and hypoplastic breasts and nipples.…”

Section: Introductionmentioning

confidence: 99%

“…A single individual with a TP63 pathogenic variant was reported with failed T‐cell receptor excision circle (TREC)‐based newborn screening was later found to have T‐cell lymphopenia. That individual was treated with intravenous immunoglobulin (IVIG) in infancy, but ultimately had normalization of T‐cell subsets and was able to stop IVIG treatment (Giampietro et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Expanding the phenotypic spectrum of TP63‐related disorders including the first set of monozygotic twins

Wenger

Liu

Harr

et al. 2017

American J of Med Genetics Pt A

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Individuals with Tumor Protein P63 (TP63)-related disorders are known to present with a range of phenotypic features, including ectrodactyly, ectodermal dysplasia, cleft lip/palate, Rapp-Hodgkin, Hay-Wells, and limb-mammary syndromes. We present six individuals from three families, including a set of monozygotic twins, with pathogenic TP63 variants who had novel clinical findings. The twins were discordant for cleft lip and palate, and the type of hand malformations, but concordant for choanal atresia, and bilateral volar nail. Both failed newborn screening for severe combined immunodeficiency (SCID) due to T-cell lymphopenia. The second family included three family members across two generations. Two of these three family members had orofacial clefting, but the remaining child had a laryngeal web and hydrocele with no clefting or hand anomalies, highlighting the variable expressivity in TP63-related disorders. The individual from the third family had unilateral cleft lip and palate, hydronephrosis, and bilateral volar nails. Together, these cases illustrate that: there is significant familial variability, including discordant major but concordant minor anomalies in the first ever reported set of molecularly confirmed monozygotic twins with pathogenic variants in TP63; pathogenic variants in TP63 should be considered in individuals with volar nail, which was previously only strongly associated with 4q34 deletion syndrome; and failed SCID newborn screening due to abnormal immune functioning may be part of the phenotypic spectrum of TP63-related disorders, as it was reported in one prior individual and two of the individuals in our case series.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expanding the phenotypic spectrum of TP63‐related disorders including the first set of monozygotic twins

Wenger

Liu

Harr

et al. 2017

American J of Med Genetics Pt A

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“…The remaining specified syndrome diagnoses included repeated instances of ataxia telangiectasia 31 and trisomy 18 (each 3%), CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital and ear abnormalities) syndrome (2%), and other rare entities as listed (Table 5). 32 …”

Section: Resultsmentioning

confidence: 99%

Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

Kwan

Abraham

Currier

et al. 2014

JAMA

614

569

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IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100 000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3 030 083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58 000 infants (95%CI, 1/46 000-1/80 000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87%(45/52), 92%(45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE Newborn screening in 11 programs in the United States identified SCID in 1 in 58 000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

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“…An appropriate evaluation, including determination of quantitative immunoglobulin levels and T-cell subset populations, may be performed in such cases to reach the diagnosis. 12 Orthopantography is done if hypodontia or dental abnormalities are present. X-ray films of hands, feet, or both may be done to demonstrate specific skeletal deformities.…”

Section: Discussionmentioning

confidence: 99%

Ectodermal dysplasia with classical clinical presentation: A rare case report

Mohan¹,

Rathore²

2020

JDPO

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Background: Ectodermal dysplasia is a syndrome consisting of heterogeneous group of hereditary malformations which have similar findings and are inherited genetically. These disorders affect the ectodermal derived tissues (hair, nails, teeth, skin and sweat glands) and lead to development of two or more tissue anomalies with heterogeneous characteristics. Case History: We report a rare case of 16 year old male presenting to us with complaints of decreased sweating, itching all over skin when exposed to sun, hypodonti, madarosis and sparse scalp hair. Thorough examination revealed classical syndromic anamolies. Skin biopsy revealed dyskeratosis and acantholysis with reduced skin adenaxae. Conclusion: Ectodermal dysplasia is a heterogeneous group of hereditary malformations and irregularities which have similar findings. Ectodermal dysplasia not only creates tissue malformations but, the quality of life of patients is also affected.

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Novel mutation in TP63 associated with ectrodactyly ectodermal dysplasia and clefting syndrome and T cell lymphopenia

Cited by 12 publications

References 11 publications

Expanding the phenotypic spectrum of TP63‐related disorders including the first set of monozygotic twins

Expanding the phenotypic spectrum of TP63‐related disorders including the first set of monozygotic twins

Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

Ectodermal dysplasia with classical clinical presentation: A rare case report

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