A girl with a unilateral cleft lip, alveolus and palate, tooth agenesis, and mild dysmorphic features, without a specific underlying syndrome diagnosis, was genotypically characterized and phenotypically described. Cleft gene panel analysis, single-nucleotide polymorphism (SNP) array, whole genome sequencing (WGS), whole exome sequencing, and quantitative PCR (Q-PCR) analysis were used as diagnostic tests. SNP array revealed a maternal deletion at 16q24.1, encompassing the cleft candidate gene USP10. WES revealed an additional de novo Loss-of-Function variant (p.(Asn838fs)) in the Zinc-Finger-Homeobox-4 (ZFHX4) gene. Q-PCR was performed to explore the effect of the ZFHX4 variant and the deletion in 16q24.1. The mRNA expression of a selection of putative target genes involved in orofacial clefting showed a lowered expression of USP10 (52%), CRISPLD2 (31%), and CRISPLD1 (1%) compared to the control. IRF6 showed no difference in gene expression. This case supports ZFHX4 as a novel cleft gene and suggests USP10 may contribute to the etiology of orofacial clefts in humans.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ajmg.a.63101 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unraveling ptosis: a comprehensive review of clinical manifestations, genetics, and treatment.
Prog Retin Eye Res
December 2024
Health Management Center, the Third Xiangya Hospital, Central South University, Changsha 410013, China; Research Center of Medical Experimental Technology, the Third Xiangya Hospital, Central South University, Changsha 410013, China; Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, Changsha 410013, China; Disease Genome Research Center, Central South University, Changsha 410013, China. Electronic address:
Ptosis is defined as an abnormally low-lying upper eyelid margin on the primary gaze, generally resulting from a congenital or acquired abnormality of the nerves or muscles that control the eyelid. Ptosis can occur alone or concurrently as an ocular or systemic syndrome, and the prevalence of ptosis varies among different countries and populations. Isolated ptosis typically causes aesthetic problems in patients and can lead to functional ophthalmic problems in severe cases.
View Article and Find Full Text PDFRole of ZFHX4 in orofacial clefting based on human genetic data and zebrafish models.
Eur J Hum Genet
December 2024
Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Orofacial clefting (OFC) is a frequent congenital anomaly and can occur either in the context of underlying syndromes or in isolation (nonsyndromic). The two common OFC phenotypes are cleft lip with/without cleft palate (CL/P) and cleft palate only (CPO). In this study, we searched for penetrant CL/P genes, by evaluating de novo copy number variants (CNV) from an exome sequencing dataset of 50 nonsyndromic patient-parent trios.
View Article and Find Full Text PDFRare nonsynonymous germline and mosaic de novo variants in Japanese patients with schizophrenia.
Psychiatry Clin Neurosci
January 2025
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Aim: Whole-exome sequencing (WES) studies have revealed that germline de novo variants (gDNVs) contribute to the genetic etiology of schizophrenia. However, the contribution of mosaic DNVs (mDNVs) to the risk of schizophrenia remains to be elucidated. In the present study, we systematically investigated the gDNVs and mDMVs that contribute to the genetic etiology of schizophrenia in a Japanese population.
View Article and Find Full Text PDFExpanding the molecular landscape of childhood apraxia of speech: evidence from a single-center experience.
Front Neurosci
September 2024
Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris Scientific Institute, Pisa, Italy.
Article Synopsis
- Childhood apraxia of speech (CAS) is a genetic speech disorder, and recent advancements in whole exome and genome sequencing have improved the identification of gene variants linked to it, particularly in a new Italian study.
- In a study of 69 Italian children with CAS, researchers used whole exome sequencing to find high-confidence and low-confidence gene variants, revealing new potential genetic links to the disorder.
- The study indicated that many of the identified high-confidence genes are involved in brain regions related to language acquisition, confirming their role in speech impairment and highlighting a significant diagnostic yield among affected Italian patients.
Loss-of-function of the Zinc Finger Homeobox 4 () gene underlies a neurodevelopmental disorder.
medRxiv
August 2024
Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium.
8q21.11 microdeletions encompassing the gene encoding transcription factor ZFHX4, have previously been associated by us with a syndromic form of intellectual disability, hypotonia, decreased balance and hearing loss. Here, we report on 57 individuals, 52 probands and 5 affected family members, with protein truncating variants (n=36), (micro)deletions (n=20) or an inversion (n=1) affecting with variable developmental delay and intellectual disability, distinctive facial characteristics, morphological abnormalities of the central nervous system, behavioral alterations, short stature, hypotonia, and occasionally cleft palate and anterior segment dysgenesis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!