@article {786, title = {Further delineation of the clinical spectrum of KAT6B disorders and allelic series of pathogenic variants.}, journal = {Genet Med}, volume = {22}, year = {2020}, month = {2020 08}, pages = {1338-1347}, abstract = {

PURPOSE: Genitopatellar syndrome and Say-Barber-Biesecker-Young-Simpson syndrome are caused by variants in the KAT6B gene and are part of a broad clinical spectrum called KAT6B disorders, whose variable expressivity is increasingly being recognized.

METHODS: We herein present the phenotypes of 32 previously unreported individuals with a molecularly confirmed diagnosis of a KAT6B disorder, report 24 new pathogenic KAT6B variants, and review phenotypic information available on all published individuals with this condition. We also suggest a classification of clinical subtypes within the KAT6B disorder spectrum.

RESULTS: We demonstrate that cerebral anomalies, optic nerve hypoplasia, neurobehavioral difficulties, and distal limb anomalies other than long thumbs and great toes, such as polydactyly, are more frequently observed than initially reported. Intestinal malrotation and its serious consequences can be present in affected individuals. Additionally, we identified four children with Pierre Robin sequence, four individuals who had increased nuchal translucency/cystic hygroma prenatally, and two fetuses with severe renal anomalies leading to renal failure. We also report an individual in which a pathogenic variant was inherited from a mildly affected parent.

CONCLUSION: Our work provides a comprehensive review and expansion of the genotypic and phenotypic spectrum of KAT6B disorders that will assist clinicians in the assessment, counseling, and management of affected individuals.

}, keywords = {Blepharophimosis, Exons, Histone Acetyltransferases, Humans, Intellectual Disability, Mutation}, issn = {1530-0366}, doi = {10.1038/s41436-020-0811-8}, author = {Zhang, Li Xin and Lemire, Gabrielle and Gonzaga-Jauregui, Claudia and Molidperee, Sirinart and Galaz-Montoya, Carolina and Liu, David S and Verloes, Alain and Shillington, Amelle G and Izumi, Kosuke and Ritter, Alyssa L and Keena, Beth and Zackai, Elaine and Li, Dong and Bhoj, Elizabeth and Tarpinian, Jennifer M and Bedoukian, Emma and Kukolich, Mary K and Innes, A Micheil and Ediae, Grace U and Sawyer, Sarah L and Nair, Karippoth Mohandas and Soumya, Para Chottil and Subbaraman, Kinattinkara R and Probst, Frank J and Bassetti, Jennifer A and Sutton, Reid V and Gibbs, Richard A and Brown, Chester and Boone, Philip M and Holm, Ingrid A and Tartaglia, Marco and Ferrero, Giovanni Battista and Niceta, Marcello and Dentici, Maria Lisa and Radio, Francesca Clementina and Keren, Boris and Wells, Constance F and Coubes, Christine and Laquerri{\`e}re, Annie and Aziza, Jacqueline and Dubucs, Charlotte and Nampoothiri, Sheela and Mowat, David and Patel, Millan S and Bracho, Ana and Cammarata-Scalisi, Francisco and Gezdirici, Alper and Fern{\'a}ndez-Ja{\'e}n, Alberto and Hauser, Natalie and Zarate, Yuri A and Bosanko, Katherine A and Dieterich, Klaus and Carey, John C and Chong, Jessica X and Nickerson, Deborah A and Bamshad, Michael J and Lee, Brendan H and Yang, Xiang-Jiao and Lupski, James R and Campeau, Philippe M} } @article {235, title = {Diagnosis of ALG12-CDG by exome sequencing in a case of severe skeletal dysplasia.}, journal = {Mol Genet Metab Rep}, volume = {1}, year = {2014}, month = {2014}, pages = {213-219}, abstract = {

Congenital Disorder of Glycosylation type Ig (ALG12-CDG) is part of a group of autosomal recessive conditions caused by deficiency of proteins involved in the assembly of dolichol-oligosaccharides used for protein N-glycosylation. In ALG12-CDG, the enzyme affected is encoded by the gene. Affected individuals present clinically with neurodevelopmental delay, growth retardation, immune deficiency, male genital hypoplasia, and cardiomyopathy. A total of six individuals have been reported in the literature. Here, we present an infant with rhizomelic short stature, talipes equinovarus, platyspondyly, and joint dislocations. The infant had marked underossification of the pubic bones. Exome sequencing was performed and two deletions, each resulting in frameshifts, were found in . A review of the literature revealed two infants with ALG12-CDG and a severe skeletal dysplasia, including under-ossification of cervical vertebrae, pubic bones, and knees; in addition to talipes equinovarus and rhizomelic short stature. The phenotype of the individual we describe resembles pseudodiastrophic dysplasia and we discuss similarities and differences between ALG12-CDG and pseudodiastrophic dysplasia. The differential diagnosis in selected undiagnosed skeletal dysplasias should include CDGs.

}, issn = {2214-4269}, doi = {10.1016/j.ymgmr.2014.04.004}, author = {Murali, Chaya and Lu, James T and Jain, Mahim and Liu, David S and Lachman, Ralph and Gibbs, Richard A and Lee, Brendan H and Cohn, Daniel and Campeau, Philippe M} }