@article {964,
	title = {Heterozygous loss of WBP11 function causes multiple congenital defects in humans and mice.},
	journal = {Hum Mol Genet},
	volume = {29},
	year = {2020},
	month = {2020 12 04},
	pages = {3662-3678},
	abstract = {<p>The genetic causes of multiple congenital anomalies are incompletely understood. Here, we report novel heterozygous predicted loss-of-function (LoF) and predicted damaging missense variants in the WW domain binding protein 11 (WBP11) gene in seven unrelated families with a variety of overlapping congenital malformations, including cardiac, vertebral, tracheo-esophageal, renal and limb defects. WBP11 encodes a component of the spliceosome with the ability to activate pre-messenger RNA splicing. We generated a Wbp11 null allele in mouse using CRISPR-Cas9 targeting. Wbp11 homozygous null embryos die prior to E8.5, indicating that Wbp11 is essential for development. Fewer Wbp11 heterozygous null mice are found than expected due to embryonic and postnatal death. Importantly, Wbp11 heterozygous null mice are small and exhibit defects in axial skeleton, kidneys and esophagus, similar to the affected individuals, supporting the role of WBP11 haploinsufficiency in the development of congenital malformations in humans. LoF WBP11 variants should be considered as a possible cause of VACTERL association as well as isolated Klippel-Feil syndrome, renal agenesis or esophageal atresia.</p>},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddaa258},
	author = {Martin, Ella M M A and Enriquez, Annabelle and Sparrow, Duncan B and Humphreys, David T and McInerney-Leo, Aideen M and Leo, Paul J and Duncan, Emma L and Iyer, Kavitha R and Greasby, Joelene A and Ip, Eddie and Giannoulatou, Eleni and Sheng, Delicia and Wohler, Elizabeth and Dimartino, Cl{\'e}mantine and Amiel, Jeanne and Capri, Yline and Lehalle, Daphn{\'e} and Mory, Adi and Wilnai, Yael and Lebenthal, Yael and Gharavi, Ali G and Krzemie{\'n}, Gra{\.z}yna G and Miklaszewska, Monika and Steiner, Robert D and Raggio, Cathy and Blank, Robert and Baris Feldman, Hagit and Milo Rasouly, Hila and Sobreira, Nara L M and Jobling, Rebekah and Gordon, Christopher T and Giampietro, Philip F and Dunwoodie, Sally L and Chapman, Gavin}
}
@article {620,
	title = {Mutations in the mitochondrial ribosomal protein MRPS22 lead to primary ovarian insufficiency.},
	journal = {Hum Mol Genet},
	volume = {27},
	year = {2018},
	month = {2018 06 01},
	pages = {1913-1926},
	abstract = {<p>Primary ovarian insufficiency (POI) is characterized by amenorrhea and loss or dysfunction of ovarian follicles prior to the age of 40. POI has been associated with autosomal recessive mutations in genes involving hormonal signaling and folliculogenesis, however, the genetic etiology of POI most often remains unknown. Here we report MRPS22 homozygous missense variants c.404G>A (p.R135Q) and c.605G>A (p.R202H) identified in four females from two independent consanguineous families as a novel genetic cause of POI in adolescents. Both missense mutations identified in MRPS22 are rare, occurred in highly evolutionarily conserved residues, and are predicted to be deleterious to protein function. In contrast to prior reports of mutations in MRPS22 associated with severe mitochondrial disease, the POI phenotype is far less severe. Consistent with this genotype-phenotype correlation, mitochondrial defects in oxidative phosphorylation or rRNA levels were not detected in fibroblasts derived from the POI patients, suggesting a non-bioenergetic or tissue-specific mitochondrial defect. Furthermore, we demonstrate in a Drosophila model that mRpS22 deficiency specifically in somatic cells of the ovary had no effect on fertility, whereas flies with mRpS22 deficiency specifically in germ cells were infertile and agametic, demonstrating a cell autonomous requirement for mRpS22 in germ cell development. These findings collectively identify that MRPS22, a component of the small mitochondrial ribosome subunit, is critical for ovarian development and may therefore provide insight into the pathophysiology and treatment of ovarian dysfunction.</p>},
	keywords = {Adolescent, Adult, Amenorrhea, Animals, Disease Models, Animal, Drosophila, Drosophila Proteins, Female, Fertility, Homozygote, Humans, Menopause, Premature, Mitochondrial Proteins, Mutation, Missense, Ovarian Follicle, Primary Ovarian Insufficiency, Ribosomal Proteins, Young Adult},
	issn = {1460-2083},
	doi = {10.1093/hmg/ddy098},
	author = {Chen, Anlu and Tiosano, Dov and Guran, Tulay and Baris, Hagit N and Bayram, Yavuz and Mory, Adi and Shapiro-Kulnane, Laura and Hodges, Craig A and Akdemir, Zeynep C and Turan, Serap and Jhangiani, Shalini N and van den Akker, Focco and Hoppel, Charles L and Salz, Helen K and Lupski, James R and Buchner, David A}
}
