@article {1435424,
	title = {ALPK1 missense pathogenic variant in five families leads to ROSAH syndrome, an ocular multisystem autosomal dominant disorder},
	journal = {Genet Med},
	volume = {21},
	number = {9},
	year = {2019},
	month = {2019 Sep},
	pages = {2103-2115},
	abstract = {PURPOSE: To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. METHODS: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members. RESULTS: We found the heterozygous missense variant in the ɑ-kinase gene, ALPK1, (c.710C\&gt;T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis. CONCLUSION: Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder.},
	issn = {1530-0366},
	doi = {10.1038/s41436-019-0476-3},
	author = {Williams, Lloyd B and Javed, Asif and Sabri, Amin and Morgan, Denise J and Huff, Chad D and Grigg, John R and Heng, Xiu Ting and Khng, Alexis J and Hollink, Iris H I M and Morrison, Margaux A and Owen, Leah A and Anderson, Katherine and Kinard, Krista and Greenlees, Rebecca and Novacic, Danica and Nida Sen, H and Zein, Wadih M and Rodgers, George M and Vitale, Albert T and Haider, Neena B and Hillmer, Axel M and Ng, Pauline C and Ng, Pauline C and Cheng, Anson and Zheng, Linda and Gillies, Mark C and van Slegtenhorst, Marjon and van Hagen, P Martin and Missotten, Tom O A R and Farley, Gary L and Polo, Michael and Malatack, James and Curtin, Julie and Martin, Frank and Arbuckle, Susan and Alexander, Stephen I and Chircop, Megan and Davila, Sonia and Digre, Kathleen B and Jamieson, Robyn V and Deangelis, Margaret M}
}
