@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 = {<p>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.</p>},
	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}
}
@article {678,
	title = {Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.},
	journal = {Am J Hum Genet},
	volume = {104},
	year = {2019},
	month = {2019 Jun 06},
	pages = {1210-1222},
	abstract = {<p>We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70\% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.</p>},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2019.03.021},
	author = {O{\textquoteright}Donnell-Luria, Anne H and Pais, Lynn S and Faundes, V{\'\i}ctor and Wood, Jordan C and Sveden, Abigail and Luria, Victor and Abou Jamra, Rami and Accogli, Andrea and Amburgey, Kimberly and Anderlid, Britt Marie and Azzarello-Burri, Silvia and Basinger, Alice A and Bianchini, Claudia and Bird, Lynne M and Buchert, Rebecca and Carr{\'e}, Wilfrid and Ceulemans, Sophia and Charles, Perrine and Cox, Helen and Culliton, Lisa and Curr{\`o}, Aurora and Demurger, Florence and Dowling, James J and Duban-Bedu, Benedicte and Dubourg, Christ{\`e}le and Eiset, Saga Elise and Escobar, Luis F and Ferrarini, Alessandra and Haack, Tobias B and Hashim, Mona and Heide, Solveig and Helbig, Katherine L and Helbig, Ingo and Heredia, Raul and H{\'e}ron, Delphine and Isidor, Bertrand and Jonasson, Amy R and Joset, Pascal and Keren, Boris and Kok, Fernando and Kroes, Hester Y and Lavillaureix, Alino{\"e} and Lu, Xin and Maas, Saskia M and Maegawa, Gustavo H B and Marcelis, Carlo L M and Mark, Paul R and Masruha, Marcelo R and McLaughlin, Heather M and McWalter, Kirsty and Melchinger, Esther U and Mercimek-Andrews, Saadet and Nava, Caroline and Pendziwiat, Manuela and Person, Richard and Ramelli, Gian Paolo and Ramos, Luiza L P and Rauch, Anita and Reavey, Caitlin and Renieri, Alessandra and Rie{\ss}, Angelika and Sanchez-Valle, Amarilis and Sattar, Shifteh and Saunders, Carol and Schwarz, Niklas and Smol, Thomas and Srour, Myriam and Steindl, Katharina and Syrbe, Steffen and Taylor, Jenny C and Telegrafi, Aida and Thiffault, Isabelle and Trauner, Doris A and van der Linden, Helio and van Koningsbruggen, Silvana and Villard, Laurent and Vogel, Ida and Vogt, Julie and Weber, Yvonne G and Wentzensen, Ingrid M and Widjaja, Elysa and Zak, Jaroslav and Baxter, Samantha and Banka, Siddharth and Rodan, Lance H}
}
