Expanding the phenotype of PPP1R21-related neurodevelopmental disorder
In this report, we present 11 additional individuals from nine unrelated families and their clinical, radiological, and molecular findings. We identified eight different variants in PPP1R21, of which six were novel variants. Global developmental delay and hypotonia are neurological features that were observed in all individuals. There is also a similar pattern of dysmorphic features with coarse faces as a gestalt observed in several individuals. Common findings in 75% of individuals with available brain imaging include delays in myelination, wavy outline of the bodies of the lateral ventricles, and slight prominence of the...
Source: Clinical Genetics - February 15, 2024 Category: Genetics & Stem Cells Authors: Mohammed Almannai Dana Marafi Maha S Zaki Reza Maroofian Stephanie Efthymiou Nebal Waill Saadi Bilal Filimban Hormos Salimi Dafsari Fatima Rahman Shazia Maqbool Eissa Faqeih Fuad Al Mutairi Hind Alsharhan Omar Abdelaty Saadoun Bin-Hasan Ruizhi Duan Mahmou Source Type: research
Prevalence and phenotypes associated with ALPK3 null variants in a large French multicentric cohort: Confirming its involvement in hypertrophic cardiomyopathy
Clin Genet. 2024 Feb 14. doi: 10.1111/cge.14505. Online ahead of print.ABSTRACTBiallelic disease-causing variants in the ALPK3 gene were first identified in children presenting with a severe cardiomyopathy. More recently, it was shown that carriers of heterozygous ALPK3 null variants are at risk of developing hypertrophic cardiomyopathy (HCM) with an adult onset. Since the number of reported ALPK3 patients is small, the mutational spectrum and clinical data are not fully described. In this multi-centric study, we described the molecular and clinical spectrum of a large cohort of ALPK3 patients. Genetic testing using target...
Source: Clinical Genetics - February 15, 2024 Category: Genetics & Stem Cells Authors: Flavie Ader Guillaume Jedraszak Alexandre Janin Clarisse Billon Nathalie Roux Buisson Adrien Bloch Meriem Bensalah Anachiara De Sandre-Giovannoli Adeline Goudal Luisa Marsili C écile Cazeneuve Philippe Charron Gilles Millat Pascale Richard Cardiogen Fren Source Type: research
Novel phenotype associated with homozygous likely pathogenic variant in the POP1 gene
Clin Genet. 2024 Feb 13. doi: 10.1111/cge.14502. Online ahead of print.ABSTRACTThe biallelic variants of the POP1 gene are associated with the anauxetic dysplasia (AAD OMIM 607095), a rare skeletal dysplasia, characterized by prenatal rhizomelic shortening of limbs and generalized joint hypermobility. Affected individuals usually have normal neurodevelopmental milestones. Here we present three cases from the same family with likely pathogenic homozygous POP1 variant and a completely novel phenotype: a girl with global developmental delay and autism, microcephaly, peculiar dysmorphic features and multiple congenital anomali...
Source: Clinical Genetics - February 14, 2024 Category: Genetics & Stem Cells Authors: Marina Michelson Keren Yosovich Sarit Bahar Yuval Yogev Ohad S Birk Mira Ginzberg Dorit Lev Source Type: research
Further evidence of involvement of ITSN1 in autosomal dominant neurodevelopmental disorder
Clin Genet. 2024 Feb 12. doi: 10.1111/cge.14497. Online ahead of print.ABSTRACTA 5-year-old affected male had following phenotypes: autism, motor stereotypy, developmental regression, staring gaze, absent speech, and behavioral abnormality. The biochemical testing was normal and genetic testing identified a de novo pathogenic variant in ITSN1 gene in the proband. To our knowledge, this is the second report that elucidates the role of ITSN1 gene in an autosomal dominant neurodevelopmental disorder.PMID:38346866 | DOI:10.1111/cge.14497 (Source: Clinical Genetics)
Source: Clinical Genetics - February 12, 2024 Category: Genetics & Stem Cells Authors: Khurram Liaqat Kayla Treat Theodore E Wilson Erin Conboy Francesco Vetrini Source Type: research
Assessing the impact of psychiatric genetic counseling on psychiatric hospitalizations
Clin Genet. 2024 Feb 11. doi: 10.1111/cge.14493. Online ahead of print.ABSTRACTPsychiatric genetic counseling (pGC) can improve patient empowerment and self-efficacy. We explored the relationship between pGC and psychiatric hospitalizations, for which no prior data exist. Using Population Data BC (a provincial dataset), we tested two hypotheses: (1) among patients (>18 years) with psychiatric conditions who received pGC between May 2010 and Dec 2016 (N = 387), compared with the year pre-pGC, in the year post-pGC there would be fewer (a) individuals hospitalized and (b) total hospital admissions; and (2) using a matched ...
Source: Clinical Genetics - February 11, 2024 Category: Genetics & Stem Cells Authors: Emily Morris Kimberlyn McGrail Sonya Cressman S Evelyn Stewart Jehannine Austin Source Type: research
A hemizygous loss-of-function variant in BCORL1 is associated with male infertility and oligoasthenoteratozoospermia
In conclusion, our findings indicate that BCORL1 is a potential candidate gene in the pathogenesis of OAT and NOA, expanded its disease spectrum and suggested that BCORL1 may play a role in spermatogenesis by interacting with SKP1.PMID:38342987 | DOI:10.1111/cge.14500 (Source: Clinical Genetics)
Source: Clinical Genetics - February 11, 2024 Category: Genetics & Stem Cells Authors: Chen Luo Zixu Chen Lanlan Meng Chen Tan Wenbin He Chaofeng Tu Juan Du Guang-Xiu Lu Ge Lin Yue-Qiu Tan Tong-Yao Hu Source Type: research
Patient perspective in perceived comparative genetic mutation risk: An exploratory review
This study aimed to address the psychological management of the impact of genetic risk on chronic diseases. We performed a systematic search of MEDLINE via PubMed, Embase, Web of Science, PsycINFO and Scopus for articles from May 2012 to August 2023. A descriptive analysis of the characteristics of the included studies was conducted. Based on the exclusion/inclusion criteria, the literature search yielded 250 studies. Seventeen full texts were assessed for eligibility and 207 articles were excluded. Observational (n = 15) and randomised clinical trials (n = 2) were examined. Most studies have been conducted on oncological ...
Source: Clinical Genetics - February 10, 2024 Category: Genetics & Stem Cells Authors: Eleonora Cilli Federica Guerra Jessica Ranieri Francesco Brancati Dina Di Giacomo Source Type: research
The first case of a point pathogenic variant in the RREB1 gene in Noonan-like Rasopathy
This study reinforces previous data on RREB1 haploinsufficiency as the driver of a new Noonan-like RASopathy variant, which includes intellectual disability, delayed motor skills, short stature, short neck, and distinctive facial dysmorphisms as key clinical indicators. These findings shed light on this RREB1-related syndrome and underscore the necessity for further investigation into the functional consequences of RREB1 mutations.PMID:38332451 | DOI:10.1111/cge.14496 (Source: Clinical Genetics)
Source: Clinical Genetics - February 9, 2024 Category: Genetics & Stem Cells Authors: Olga Shatokhina Fatima Bostanova Maria Bulakh Anastasia Beresneva Oxana Ryzhkova Source Type: research
Feasibility of whole-exome sequencing in fine-needle aspiration specimens of papillary thyroid microcarcinoma for the identification of novel gene mutations
This study aimed to evaluate the feasibility of WES using FNA specimens of PTMC. Five PTMC patients were enrolled with clinical characteristics gathered. Fine aspiration cytology needle (23 gauges) was used to collect FNA biopsy with ultrasound guidance. WES analysis of FNA specimens from five PTMC patients and matched blood samples was performed. The WES of FNA samples yielded an average sequencing depth of 281× and average coverage of 99.5%. We identified 534 somatic single-nucleotide variants and 13 indels in total, and per sample, we found a mean of 24 exonic mutations, which affected a total of 120 genes. In the PTMC...
Source: Clinical Genetics - February 8, 2024 Category: Genetics & Stem Cells Authors: Liyuan Ma Luying Gao Ya Hu Xiaoyi Li Chunhao Liu Jiang Ji Xinlong Shi Aonan Pan Yuang An Nengwen Luo Yu Xia Yuxin Jiang Source Type: research
Identification of a founder variant AAGAB c.370C & gt;T, p.Arg124Ter in patients with punctate palmoplantar keratoderma in Southern Denmark
This study confirms that the frequently observed variant AAGAB c.370C>T, p.Arg124Ter in punctate PPK among patients in the Region of Southern Denmark is caused by a founder variant. We recommend testing for the variant as initial screening in our region and potentially for all Danish patients presenting with punctate PPK.PMID:38311882 | DOI:10.1111/cge.14486 (Source: Clinical Genetics)
Source: Clinical Genetics - February 5, 2024 Category: Genetics & Stem Cells Authors: Stine Bj ørn Gram Anne Sofie Fredberg J ørgensen Anette Bygum Klaus Brusgaard Lilian Bomme Ousager Source Type: research
Contribution of genetic variants in the development of familial premature coronary artery disease in a cohort of cardiac patients
Clin Genet. 2024 Feb 3. doi: 10.1111/cge.14491. Online ahead of print.ABSTRACTCoronary artery disease (CAD), the most prevalent cardiovascular disease, is the leading cause of death worldwide. Heritable factors play a significant role in the pathogenesis of CAD. It has been proposed that approximately one-third of patients with CAD have a positive family history, and individuals with such history are at ~1.5-fold increased risk of CAD in their lifespans. Accordingly, the long-recognized familial clustering of CAD is a strong risk factor for this disease. Our study aimed to identify candidate genetic variants contributing t...
Source: Clinical Genetics - February 3, 2024 Category: Genetics & Stem Cells Authors: Sepideh Mehvari Nahid Karimian Fathi Sara Saki Maryam Asadnezhad Sanaz Arzhangi Fatemeh Ghodratpour Marzieh Mohseni Farzane Zare Ashrafi Saeed Sadeghian Mohammadali Boroumand Fatemeh Shokohizadeh Elham Rostami Rahnama Boroumand Reza Najafipour Reza Malekz Source Type: research
Further description of two individuals with de novo p.(Glu127Lys) missense variant in the ASCL1 gene
We report two additional unrelated individuals sharing the same sporadic ASCL1 p.(Glu127Lys) missense variant in the bHLH domain and a common phenotype with short-segment HSCR, signs of dysautonomia, and developmental delay. One has also mild CCHS without polyalanine expansion in PHOX2B, compatible with the diagnosis of Haddad syndrome. Furthermore, missense variants with homologous position in the same bHLH domain in other genes are known to cause human diseases. The description of additional individuals carrying the same variant and similar phenotype, as well as targeted functional studies, would be interesting to furthe...
Source: Clinical Genetics - January 30, 2024 Category: Genetics & Stem Cells Authors: Marl ène Malbos Emma Wakeling Thierry Gautier Odile Boespflug-Tanguy Louise Busby Tashunka Taylor-Miller Benjamin Dudoignon Plamen Bokov J érôme Govin Margot Grisval Ad élaïde Rega Marie-Gabrielle Mourot De Rougemont Marie-H élène Aubriot-Lorton V Source Type: research
Clinical and molecular characteristics of 26 fetuses with lethal multiple congenital contractures
Clin Genet. 2024 Jan 26. doi: 10.1111/cge.14490. Online ahead of print.ABSTRACTMultiple congenital contractures (MCC) due to fetal akinesia manifest across a broad spectrum of diseases, ranging from mild distal arthrogryposis to lethal fetal akinesia deformation sequence. We hereby present a series of 26 fetuses displaying severe MCC phenotypes from 18 families and describe detailed prenatal ultrasound findings, postmortem clinical evaluations, and genetic investigations. Most common prenatal findings were abnormal facial profile (65%), central nervous system abnormalities (62%), polyhydramnios (50%), increased nuchal tran...
Source: Clinical Genetics - January 26, 2024 Category: Genetics & Stem Cells Authors: Gozde Tutku Turgut Umut Altunoglu Cagri Gulec Tugba Sarac Sivrikoz Tu ğba Kalaycı Guven Toksoy Şahin Avcı Behiye Tu ğçe Yıldırım G özde Yeşil Sayın Ibrahim Halil Kalelioglu Birsen Karaman Recep Has Seher Ba şaran Atil Yuksel H ülya Kayserili Source Type: research
Development of disease-specific growth charts for Korean children with Beckwith-Wiedemann syndrome
Clin Genet. 2024 Jan 24. doi: 10.1111/cge.14488. Online ahead of print.ABSTRACTBeckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth syndrome. Despite its distinctive growth pattern, the detailed growth trajectories of children with BWS remain largely unknown. We retrospectively analyzed 413 anthropometric measurements over an average of 4.4 years of follow-up in 51 children with BWS. We constructed sex-specific percentile curves for height, weight, and head circumference using a generalized additive model for location, scale, and shape. Males with BWS exhibited greater height at all ages evaluated, weight before t...
Source: Clinical Genetics - January 24, 2024 Category: Genetics & Stem Cells Authors: Naye Choi Hwa Young Kim Jung Min Ko Source Type: research
Genotype-phenotype correlation in Prader-Willi syndrome: A large-sample analysis in China
Clin Genet. 2024 Jan 23. doi: 10.1111/cge.14477. Online ahead of print.ABSTRACTThe genotype-phenotype relationship in PWS patients is important for a better understanding of the clinical phenotype and clinical characteristics of different genotypes of PWS in children. We aimed to explore the influence of specific gene changes on the clinical symptoms of PWS and the value of early screening and early intervention of the condition. All data in this study were extracted from the database of the XiaoPang Weili Rare Disease Care Center. The collected information included basic demographics, maternal pregnancy information, endoc...
Source: Clinical Genetics - January 23, 2024 Category: Genetics & Stem Cells Authors: Shujiong Mao Lili Yang Ying Gao Chaochun Zou Source Type: research
