@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 {714, title = {Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita.}, journal = {Hum Mutat}, volume = {40}, year = {2019}, month = {2019 12}, pages = {2270-2285}, abstract = {

Pathogenic variants in the X-linked gene ZC4H2, which encodes a zinc-finger protein, cause an infrequently described syndromic form of arthrogryposis multiplex congenita (AMC) with central and peripheral nervous system involvement. We present genetic and detailed phenotypic information on 23 newly identified families and simplex cases that include 19 affected females from 18 families and 14 affected males from nine families. Of note, the 15 females with deleterious de novo ZC4H2 variants presented with phenotypes ranging from mild to severe, and their clinical features overlapped with those seen in affected males. By contrast, of the nine carrier females with inherited ZC4H2 missense variants that were deleterious in affected male relatives, four were symptomatic. We also compared clinical phenotypes with previously published cases of both sexes and provide an overview on 48 males and 57 females from 42 families. The spectrum of ZC4H2 defects comprises novel and recurrent mostly inherited missense variants in affected males, and de novo splicing, frameshift, nonsense, and partial ZC4H2 deletions in affected females. Pathogenicity of two newly identified missense variants was further supported by studies in zebrafish. We propose ZC4H2 as a good candidate for early genetic testing of males and females with a clinical suspicion of fetal hypo-/akinesia and/or (neurogenic) AMC.

}, issn = {1098-1004}, doi = {10.1002/humu.23841}, author = {Frints, Suzanna G M and Hennig, Friederike and Colombo, Roberto and Jacquemont, Sebastien and Terhal, Paulien and Zimmerman, Holly H and Hunt, David and Mendelsohn, Bryce A and Korda{\ss}, Ulrike and Webster, Richard and Sinnema, Margje and Abdul-Rahman, Omar and Suckow, Vanessa and Fern{\'a}ndez-Ja{\'e}n, Alberto and van Roozendaal, Kees and Stevens, Servi J C and Macville, Merryn V E and Al-Nasiry, Salwan and van Gassen, Koen and Utzig, Norbert and Koudijs, Suzanne M and McGregor, Lesley and Maas, Saskia M and Baralle, Diana and Dixit, Abhijit and Wieacker, Peter and Lee, Marcus and Lee, Arthur S and Engle, Elizabeth C and Houge, Gunnar and Gradek, Gyri A and Douglas, Andrew G L and Longman, Cheryl and Joss, Shelagh and Velasco, Danita and Hennekam, Raoul C and Hirata, Hiromi and Kalscheuer, Vera M} }