Rare missense variant p.Ala505Ser in the ZAK protein observed in a patient with split-hand/foot malformation from a non-consanguineous pedigree

Funk, Christopher Ronald; Huey, Elizabeth S; May, Melanie; Peng, Yunhui; Michonova, Ekaterina; Best, Robert G.; Schwartz, Charles E.; Blenda, Anna V.

doi:10.1177/0300060519879293

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…Spielmann et al 26 have found that Map3k20 , a gene within the deletion region, is expressed in developing limbs. Furthermore, the authors summarized the clinical manifestations of Map3k20 mutations, including split‐foot malformation with mesoaxial polydactyly, which is related to hearing loss and exhibits a possible clinical phenotype of cutaneous syndactyly 26,27 . Herein, cutaneous syndactyly was an important malformation in the examined fetus.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the authors summarized the clinical manifestations of Map3k20 mutations, including split-foot malformation with mesoaxial polydactyly, which is related to hearing loss and exhibits a possible clinical phenotype of cutaneous syndactyly. 26,27 Herein, cutaneous syndactyly was an important malformation in the examined fetus. However, according to mouse experiments and reported pedigrees, the heterozygous deletion of Map3k20 did not induce abnormal morphological changes.…”

Section: Clinical Datamentioning

confidence: 99%

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A novel chromosome 2q24.3‐q32.1 microdeletion in a fetus with multiple malformations

Zhu

Wang

Guan

et al. 2022

Clinical Laboratory Analysis

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Background Terminal or interstitial deletion of chromosome 2q is rarely reported but clinically significant, which can result in developmental malformations and psychomotor retardation in humans. In the present study, we analyzed this deletion to comprehensively clarify the relationship between phenotype and microdeletion region. Methods We collected clinical records of the fetus and summarized patient symptoms. Subsequently, genomic DNA was extracted from fetal tissue or peripheral blood collected from parents. In addition, whole‐exome sequencing (WES) and copy number variation sequencing (CNV‐seq) were performed. Results The fetus presented a previously unreported interstitial deletion of 2q24.3‐q32.1. WES and CNV‐seq revealed a de novo 18.46 Mb deletion at 2q24.3‐q32.1, a region involving 94 protein‐coding genes, including HOXD13, MAP3K20, DLX1, DLX2, SCN2A, and SCN1A. The fetus had upper and lower limb malformations, including camptodactyly and syndactyly, along with congenital cardiac defects. Conclusion Herein, we report a fetus with a novel microdeletion of chromosome 2q24.3‐q32.1, likely a heterozygous pathogenic variant. Haploinsufficiency of HOXD13 might be related to limb deformity in the fetus.

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Section: Discussionmentioning

confidence: 99%

Section: Clinical Datamentioning

confidence: 99%

A novel chromosome 2q24.3‐q32.1 microdeletion in a fetus with multiple malformations

Zhu

Wang

Guan

et al. 2022

Clinical Laboratory Analysis

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Heterozygous MAP3K20 variants cause ectodermal dysplasia, craniosynostosis, sensorineural hearing loss, and limb anomalies

Brooks,

Burke,

Lee

et al. 2024

Hum. Genet.

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Variable clinical presentation of split hand/foot malformation syndrome in a family with microduplication of 10q24.32: a case report

Akimova,

Markova,

Ampleeva

et al. 2024

Front. Genet.

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SHFM (Split Hand/Foot Malformation) is a heterogeneous group of disorders characterized by the presence of clefts in the hands and feet, along with syndactyly of the digits. In this article, we describe a family in which two members exhibit characteristic developmental abnormalities associated with SHFM, presenting with variable clinical features. Using whole-genome sequencing, we identified a microduplication of a chromosomal segment on locus 10q24.32, specifically spanning positions 102934495 to 103496555, encompassing genes BTRC, POLL, FBXW4 and LBX1 in the proband. Genomic duplications, including these genes, were previously described in patients diagnosed with the third type of SHFM. We validated the presence of this structural rearrangement in 7 family members, including the proband and the proband’s father. Remarkably, further investigation demonstrated that the detected duplication exhibits a mosaic state in the phenotypically normal paternal grandmother of the proband, thereby providing a plausible explanation for the absence of a pathological phenotype in her.

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Rare missense variant p.Ala505Ser in the ZAK protein observed in a patient with split-hand/foot malformation from a non-consanguineous pedigree

Cited by 3 publications

References 21 publications

A novel chromosome 2q24.3‐q32.1 microdeletion in a fetus with multiple malformations

A novel chromosome 2q24.3‐q32.1 microdeletion in a fetus with multiple malformations

Heterozygous MAP3K20 variants cause ectodermal dysplasia, craniosynostosis, sensorineural hearing loss, and limb anomalies

Variable clinical presentation of split hand/foot malformation syndrome in a family with microduplication of 10q24.32: a case report

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