Article
Genetics & Heredity
Onochie Okoye, Jenina Capasso, Sarina M. Kopinsky, Louise Amlie-Wolf, Alex V. Levin, Adele Schneider
Summary: SOX2 pathogenic variants are the most common known genetic cause of clinical anophthalmia and microphthalmia. However, patients without major ocular malformation but with multi-system developmental disorders have been reported, indicating a broader range of clinical phenotypes. Our study suggests that there is no discernible pattern to distinguish patients with normal eyes. Our findings further expand the phenotypic spectrum of SOX2 mutations and challenge the classification of SOX2 disorder as solely an anophthalmia/microphthalmia syndrome. Considering SOX2 pathogenic variants in individuals with normal eyes is important for differential diagnoses, given the various combinations of features associated with this condition.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Biochemistry & Molecular Biology
Dulce Lima Cunha, Nicholas Owen, Vijay Tailor, Marta Corton, Maria Theodorou, Mariya Moosajee
Summary: This study identified two missense variants in the paired domain of the PAX6 gene leading to isolated foveal hypoplasia with nystagmus in two independent families. It also provided evidence of paternal postzygotic mosaicism as the cause of inheritance, highlighting the importance of genetic counseling and family planning in cases ofPAX6variants.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Li-Hong Wu, Qiao Zheng, Miao He, Li-He Zhang, Liu Du, Hong-Ning Xie
Summary: This study aimed to establish normal fetal size ranges of optic chiasm, optic nerves, and optic tracts using ultrasound and compare them with fetuses with anophthalmia/microphthalmia. Normal widths increased linearly with gestational age while optic nerve width in affected fetuses was significantly smaller. This suggests fetal anophthalmia/microphthalmia may be associated with optic nerve hypoplasia.
QUANTITATIVE IMAGING IN MEDICINE AND SURGERY
(2021)
Article
Medicine, General & Internal
Yoshiro Yoshikawa, Chikashi Yamakawa, Takanao Shimabukuro, Hideo Kinjo, Shogo Fukase, Hiromichi Oshiro, Ryo Katsuki, Yasunori Tome, Kotaro Nishida
Summary: This is a case report on a syndrome characterized by abnormal eye development and limb anomalies. The patient initially presented with scoliosis, which progressively worsened over four years. A surgical treatment was performed to preserve the balance of standing and sitting, and significant improvement was observed.
Article
Biochemistry & Molecular Biology
Violeta Trejo-Reveles, Nicholas Owen, Brian Ho Ching Chan, Maria Toms, Jeffrey J. Schoenebeck, Mariya Moosajee, Joe Rainger, Genom England Research Consortium
Summary: Ocular coloboma (OC) is a tissue defect in the ventral eye caused by incomplete optic fissure closure during embryonic development. This study identified 10 candidate genes, including EMX2, NID1, and EPHB3, that are involved in ventral eye development across multiple vertebrate species. Manipulation of emx2 and ephb3 in zebrafish embryos resulted in the developmental OC phenotype. These findings suggest that further analysis of EMX2, NID1, and EPHB3 is warranted in the context of ocular coloboma and structural eye malformations.
Article
Endocrinology & Metabolism
Louise C. Gregory, Peter Gergics, Marilena Nakaguma, Hironori Bando, Giuseppa Patti, Mark J. McCabe, Qing Fang, Qianyi Ma, Ayse Bilge Ozel, Jun Z. Li, Michele Moreira Poina, Alexander A. L. Jorge, Anna F. Figueredo Benedetti, Antonio M. Lerario, Ivo J. P. Arnhold, Berenice B. Mendonca, Mohamad Maghnie, Sally A. Camper, Luciani R. S. Carvalho, Mehul T. Dattani
Summary: OTX2 mutations are rarely associated with isolated hypopituitarism without eye abnormalities, with variable penetrance even within the same pedigree. Our data suggest that endocrine phenotypes in patients with OTX2 mutations originate from the hypothalamus, with OTX2 expression in multiple brain regions during human embryogenesis.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2021)
Article
Genetics & Heredity
Pierre K. Boerkoel, Katherine Dixon, Carrie Fitzsimons, Yaoqing Shen, Stephanie Huynh, Kamilla Schlade-Bartusiak, Luka Culibrk, Simon Chan, Cornelius F. Boerkoel, Steven J. M. Jones, Hui-Lin Chin
Summary: This study reports a newborn with syndromic degenerative anophthalmia and a complex de novo rearrangement of chromosome 13q. Long-read genome sequencing improved the resolution and clinical interpretation of the rearrangement, providing new insights into the molecular etiology of MAC.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Review
Genetics & Heredity
Louise Amlie-Wolf, Tanya Bardakjian, Sarina M. Kopinsky, Linda M. Reis, Elena Semina, Adele Schneider
Summary: SOX2 variants and deletions are common causes of anophthalmia and microphthalmia. Patients with SOX2 variants often present with intellectual disability, seizures, and brain anomalies. Recommendations for newly diagnosed patients include eye exams, brain MRIs, and endocrine and neurology examinations.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Surgery
Isabella Parizotto Paula, Raul Goncalves Paula, Nancy Mizue Kokitsu, Nivaldo Alonso, Cristiano Tonello
Summary: This study investigated the frequency of anophthalmia and microphthalmia in patients with craniofacial anomalies (FCAs). The results showed that anophthalmia was more common than microphthalmia and was more likely to be accompanied by FCAs. Cleft lip and palate were the most frequent associated malformations.
JOURNAL OF CRANIOFACIAL SURGERY
(2023)
Article
Genetics & Heredity
Rabia Basharat, Kim Rodenburg, Maria Rodriguez-Hidalgo, Afeefa Jarral, Ehsan Ullah, Jordi Corominas, Christian Gilissen, Syeda Tatheer Zehra, Usman Hameed, Muhammad Ansar, Suzanne E. de Bruijn
Summary: This study performed genome sequencing on families affected by anophthalmia and microphthalmia, and identified known and novel genetic variants associated with these disorders. The findings highlight the importance of genome sequencing for accurate diagnosis and the role of non-coding variants in these eye disorders.
Article
Ophthalmology
Jeremy M. Schraw, Renata H. Benjamin, Daryl A. Scott, Brian P. Brooks, Robert B. Hufnagel, Scott D. McLean, Hope Northrup, Peter H. Langlois, Mark A. Canfield, Angela E. Scheuerle, Christian P. Schaaf, Joseph W. Ray, Han Chen, Michael D. Swartz, Laura E. Mitchell, A. J. Agopian, Philip J. Lupo
Summary: This study analyzed 653 cases of anophthalmia/microphthalmia identified by the Texas Birth Defects Registry from 1999 to 2014, and found 111 different birth defect combinations, with those involving central nervous system defects, head/neck defects, and orofacial clefts being the most common. The study suggests the importance of further research into the potential susceptibility patterns and malformation syndromes associated with anophthalmia/microphthalmia.
OPHTHALMIC EPIDEMIOLOGY
(2021)
Article
Ophthalmology
Yong Joon Kim, Hyo Song Park, Jeonghwan Youk, Jung Woo Han, Suk Ho Byeon, Sung Soo Kim, Young Seok Ju, Christopher Seungkyu Lee
Summary: This study found that some retinoblastoma patients carry germline BRCA1/2 family variants, which may be associated with the development of retinoblastoma along with RB1 mutations.
BRITISH JOURNAL OF OPHTHALMOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Antonella Riva, Antonella Gambadauro, Valeria Dipasquale, Celeste Casto, Maria Domenica Ceravolo, Andrea Accogli, Marcello Scala, Giorgia Ceravolo, Michele Iacomino, Federico Zara, Pasquale Striano, Caterina Cuppari, Gabriella Di Rosa, Maria Concetta Cutrupi, Vincenzo Salpietro, Roberto Chimenz
Summary: MAC is a group of congenital eye anomalies that can affect one or both eyes. Variants in the KIF17 gene may be associated with microphthalmia and coloboma, highlighting a potential conserved role of this gene in eye development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Dentistry, Oral Surgery & Medicine
Theodosia Bartzela, Bjoern Theuerkauf, Elisabeth Reichardt, Malte Spielmann, Charlotte Opitz
Summary: The study clinically characterized patients and family members with cleft lip and/or palate and associated congenital malformations or syndromes, proposing possible inheritance patterns. Results showed that there was individual and interfamilial phenotypic variability in patients with CL/P, making understanding of etiopathogenesis challenging.
CLINICAL ORAL INVESTIGATIONS
(2021)
Article
Genetics & Heredity
Marie Boisson, Anne-Gael Cordier, Jelena Martinovic, Aline Receveur, Aurelie Mouka, Romain Diot, Catherine Egoroff, Geoffroy Esnault, Loic Drevillon, Alexandra Benachi, Gerard Tachdjian, Lucie Tosca
Summary: This study retrospectively analyzed copy number variations (CNVs) in fetuses and newborns with congenital diaphragmatic hernia (CDH) using high-resolution array comparative genomic hybridization (array-CGH). The findings identified potential candidate genes related to CDH occurrence, providing the possibility for new methods of a positive diagnosis.
PRENATAL DIAGNOSIS
(2022)
Editorial Material
Genetics & Heredity
Anne M. Slavotinek, Benjamin D. Solomon
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2020)
Article
Genetics & Heredity
Karly Hampshire, Pierre-Marie Martin, Colleen Carlston, Anne Slavotinek
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2020)
Article
Genetics & Heredity
Anne H. Mardy, Ugur Hodoglugil, Tiffany Yip, Anne M. Slavotinek
Summary: Bardet-Biedl syndrome (BBS) is a rare ciliopathy with specific genetic features, characterized by early onset retinal dystrophy, polydactyly, and obesity. The IFT74 gene may play a key role in the diagnosis of BBS.
Article
Genetics & Heredity
Katherine E. Donohue, Catherine Gooch, Alexander Katz, Jessica Wakelee, Anne Slavotinek, Bruce R. Korf
Summary: The interpretation of genetic testing results is prone to errors, with professionals facing challenges and pitfalls in interpretation. Misinterpretation can lead to unnecessary follow-up tests and incorrect clinical management.
Article
Genetics & Heredity
Justin O. Szot, Anne Slavotinek, Karen Chong, Oliver Brandau, Marjan Nezarati, Anna M. Cueto-Gonzalez, Millan S. Patel, Walter P. Devine, Shannon Rego, Alicia P. Acyinena, Patrick Shannon, Diane Myles-Reid, Susan Blaser, Tim V. Mieghem, Halenur Yavuz-Kienle, Heyko Skladny, Kristen Miller, Miereia D. T. Riera, Silvia A. Martinez, Eduardo F. Tizzano, Lucie Dupuis, Dimitri James Stavropoulos, Vanda McNiven, Roberto Mendoza-Londono, Alison M. Elliott, Robert S. Phillips, Gavin Chapman, Sally L. Dunwoodie
Summary: NAD is a vital coenzyme synthesized from dietary l-tryptophan during embryogenesis. In patients with variants in KYNU, HAAO, and NADSYN1 genes, disruption of NAD synthesis leads to multiple malformations of the heart, kidney, vertebrae, and limbs. Misssense mutations have been identified as a cause of malformation, resulting in moderate to severe NAD deficiency.
Article
Genetics & Heredity
Joseph T. Shieh, Monica Penon-Portmann, Karen H. Y. Wong, Michal Levy-Sakin, Michelle Verghese, Anne Slavotinek, Renata C. Gallagher, Bryce A. Mendelsohn, Jessica Tenney, Daniah Beleford, Hazel Perry, Stephen K. Chow, Andrew G. Sharo, Steven E. Brenner, Zhongxia Qi, Jingwei Yu, Ophir D. Klein, David Martin, Pui-Yan Kwok, Dario Boffelli
Summary: Current genetic tests have limited diagnostic capabilities for rare diseases, but the Full-Genome Analysis method (FGA) can detect small and structural variants with a higher diagnostic yield. FGA has the potential to improve variant detection and provide higher resolution genome maps for future applications.
NPJ GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Anne Slavotinek, Mathilde Lefebvre, Anne-Claire Brehin, Christel Thauvin, Sophie Patrier, Teresa N. Sparks, Mary Norton, Jingwei Yu, Eric Huang
Summary: Variants in the ARID1A gene are associated with Coffin-Siris syndrome, leading to severe developmental delays and a range of malformations in fetuses and neonates. These variants can affect the expression of important genes, potentially leading to brain malformations and other abnormalities.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Article
Genetics & Heredity
Mari Minatogawa, Ai Unzaki, Hiroko Morisaki, Delfien Syx, Tohru Sonoda, Andreas R. Janecke, Anne Slavotinek, Nicol C. Voermans, Yves Lacassie, Roberto Mendoza-Londono, Klaas J. Wierenga, Parul Jayakar, William A. Gahl, Cynthia J. Tifft, Luis E. Figuera, Yvonne Hilhorst-Hofstee, Alessandra Maugeri, Ken Ishikawa, Tomoko Kobayashi, Yoko Aoki, Toshihiro Ohura, Hiroshi Kawame, Michihiro Kono, Kosuke Mochida, Chiho Tokorodani, Kiyoshi Kikkawa, Takayuki Morisaki, Tetsuyuki Kobayashi, Takaya Nakane, Akiharu Kubo, Judith D. Ranells, Ohsuke Migita, Glenda Sobey, Anupriya Kaur, Masumi Ishikawa, Tomomi Yamaguchi, Naomichi Matsumoto, Fransiska Malfait, Noriko Miyake, Tomoki Kosho
Summary: This study systematically investigated Musculocontractural Ehlers-Danlos syndrome caused by biallelic loss-of-function variants in CHST14, revealing it as a multisystem disorder with unique clinical phenotypes consisting of multiple malformations and progressive fragility-related manifestations requiring lifelong, multidisciplinary healthcare approaches.
JOURNAL OF MEDICAL GENETICS
(2022)
Correction
Genetics & Heredity
Joseph T. Shieh, Monica Penon-Portmann, Karen H. Y. Wong, Michal Levy-Sakin, Michelle Verghese, Anne Slavotinek, Renata C. Gallagher, Bryce A. Mendelsohn, Jessica Tenney, Daniah Beleford, Hazel Perry, Stephen K. Chow, Andrew G. Sharo, Steven E. Brenner, Zhongxia Qi, Jingwei Yu, Ophir D. Klein, David Martin, Pui-Yan Kwok, Dario Boffelli
NPJ GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Jirat Chenbhanich, Anne Slavotinek, Allison Tam
Summary: This study aimed to understand the impact of the COVID-19 pandemic on the well-being, clinical training, and medical education of clinical trainees in medical genetics and genomics residency and fellowship programs. The survey results showed negative effects on trainees' well-being and clinical training, with increased utilization of telehealth but also challenges. Further research is needed to optimize the integration of lessons learned into the training of medical genetics and genomics in the post-pandemic era.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Hannah Kortbawi, Elizabeth Ames, Amanda Pritchard, Patrick Devine, Jessica van Ziffle, Anne Slavotinek
Summary: Congenital nicotinamide adenine dinucleotide (NAD) deficiency disorders are associated with pathogenic variants in NADSYN1, HAAO, and KYNU genes, causing a range of anomalies including those seen in VATER/VACTERL association. Patients often face premature death, while survivors may experience developmental delays or intellectual disability.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Genetics & Heredity
Anne Slavotinek, Hannah Prasad, Tiffany Yip, Shannon Rego, Hannah Hoban, Mark Kvale
Summary: The interpretation of genomic variants can be improved by using human phenotype ontology (HPO) terms to standardize clinical features and predict causative genes. In this study, whole exome sequencing was performed on 453 pediatric patients, resulting in the identification of pathogenic or likely pathogenic variants. The use of Phen2Gene software with HPO terms allowed for the ranking of causative genes, with genes associated with well-characterized phenotypes and deep HPO terms having the highest rankings. These findings have implications for prioritizing candidate genes in clinical and laboratory settings.
Article
Genetics & Heredity
Monica Penon-Portmann, Ugur Hodoglugil, Arun P. Wiita, Tiffany Yip, Anne Slavotinek, Jessica L. Tenney
Summary: Loss-of-function biallelic variants in TRAPPC9 are associated with an intellectual disability syndrome, and this study describes a patient with neurodevelopmental disorders and a pathogenic deletion in the TRAPPC9 gene.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Kristen Wigby, Monia Hammer, Mari Tokita, Priyanka Patel, Marilyn C. C. Jones, Austin Larson, Frances Velez Bartolomei, Natalie Dykzeul, Anne Slavotinek, Tiffany Yip, Sara Bandres-Ciga, Brittany N. N. Simpson, Kristen Suhrie, Suma Shankar, Regan Veith, Jennifer Bragg, Cynthia Powell, Stephen F. F. Kingsmore, David Dimmock, Jill Maron, Jonathan Davis, Miguel Del Campo
Summary: The use of unbiased genomic sequencing in critically ill infants with rare diseases such as Kabuki syndrome (KS) can provide valuable insights. This study retrospectively reviewed medical records of infants diagnosed with KS through genome-wide sequencing. Analysis of genomic data identified common phenotypic features and resulted in changes in management. Early use of unbiased genome-wide sequencing enabled molecular diagnosis prior to clinical recognition, expanding the understanding of KS and its phenotypic spectrum.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Anne Slavotinek, Hannah Prasad, Simon Outram, Sarah Scollon, Shannon Rego, Tiffany Yip, Hannah Hoban, Kate M. Foreman, Whitley Kelley, Candice Finnila, Jonathan Berg, Priyanka Murali, Katherine E. Bonini, Lisa J. Martin, Adam Hott
Summary: Accurate and understandable information after genetic testing is crucial for patients and professionals. The study highlights the importance of information from genetics professionals and healthcare workers, as well as the internet. It also emphasizes the challenges of finding helpful information for individuals with uncertain or negative results, and the need to reach non-English speakers.
GENETICS IN MEDICINE
(2023)
