@article {436, title = {Additional features of Gillespie syndrome in two Brazilian siblings with a novel ITPR1 homozygous pathogenic variant.}, journal = {Eur J Med Genet}, volume = {61}, year = {2018}, month = {2018 Mar}, pages = {134-138}, abstract = {

Gillespie syndrome (GS) [MIM: 206700] is a very rare condition characterized by bilateral iris defect, congenital hypotonia, cerebellar ataxia and intellectual disability. The typical iris anomaly is considered necessary to the diagnosis of GS. Recently, variants in ITPR1 were described causing GS. Non-neurological features were reported in few patients. Here we describe two consanguineous siblings with GS and a novel homozygous ITPR1 pathogenic variant (p.N984fs). They also present a cardiac defect (pulmonary valve stenosis) and one sib had a genitourinary malformation (ureteropelvic junction obstruction). Our report reinforces ITPR1 as the cause of GS and suggests a possible role of ITPR1 in the development of other organs.

}, keywords = {Aniridia, Brazil, Cerebellar Ataxia, Child, Preschool, Consanguinity, Female, Homozygote, Humans, Infant, Inositol 1,4,5-Trisphosphate Receptors, Intellectual Disability, Male, Mutation, Pedigree, Siblings}, issn = {1878-0849}, doi = {10.1016/j.ejmg.2017.11.005}, author = {Carvalho, Daniel R and Medeiros, Jo{\~a}o Eugenio G and Ribeiro, Daniela Sebestyan M and Martins, Bernardo J A F and Sobreira, Nara L M} } @article {427, title = {Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome.}, journal = {Am J Med Genet A}, volume = {173}, year = {2017}, month = {2017 Oct}, pages = {2763-2771}, abstract = {

Horstick et al. (2013) previously reported a homozygous p.Trp284Ser variant in STAC3 as the cause of Native American myopathy (NAM) in 5 Lumbee Native American families with congenital hypotonia and weakness, cleft palate, short stature, ptosis, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH). Here we present two non-Native American families, who were found to have STAC3 pathogenic variants. The first proband and her affected older sister are from a consanguineous Qatari family with a suspected clinical diagnosis of Carey-Fineman-Ziter syndrome (CFZS) based on features of hypotonia, myopathic facies with generalized weakness, ptosis, normal extraocular movements, cleft palate, growth delay, and kyphoscoliosis. We identified the homozygous c.851G>C;p.Trp284Ser variant in STAC3 in both sisters. The second proband and his affected sister are from a non-consanguineous, Puerto Rican family who was evaluated for a possible diagnosis of Moebius syndrome (MBS). His features included facial and generalized weakness, minimal limitation of horizontal gaze, cleft palate, and hypotonia, and he has a history of MH. The siblings were identified to be compound heterozygous for STAC3 variants c.851G>C;p.Trp284Ser and c.763_766delCTCT;p.Leu255IlefsX58. Given the phenotypic overlap of individuals with CFZS, MBS, and NAM, we screened STAC3 in 12 individuals diagnosed with CFZS and in 50 individuals diagnosed with MBS or a congenital facial weakness disorder. We did not identify any rare coding variants in STAC3. NAM should be considered in patients presenting with facial and generalized weakness, normal or mildly abnormal extraocular movement, hypotonia, cleft palate, and scoliosis, particularly if there is a history of MH.

}, keywords = {Adaptor Proteins, Signal Transducing, Adolescent, Adult, Child, Female, Humans, Male, Mobius Syndrome, Muscular Diseases, Mutation, Pedigree, Pierre Robin Syndrome, Prognosis, Young Adult}, issn = {1552-4833}, doi = {10.1002/ajmg.a.38375}, author = {Telegrafi, Aida and Webb, Bryn D and Robbins, Sarah M and Speck-Martins, Carlos E and FitzPatrick, David and Fleming, Leah and Redett, Richard and Dufke, Andreas and Houge, Gunnar and van Harssel, Jeske J T and Verloes, Alain and Robles, Angela and Manoli, Irini and Engle, Elizabeth C and Jabs, Ethylin W and Valle, David and Carey, John and Hoover-Fong, Julie E and Sobreira, Nara L M} } @article {269, title = {Sclerocornea in a patient with van den Ende-Gupta syndrome homozygous for a SCARF2 microdeletion.}, journal = {Am J Med Genet A}, volume = {164A}, year = {2014}, month = {2014 May}, pages = {1170-4}, abstract = {

Van den Ende-Gupta Syndrome (VDEGS) is an autosomal recessive disorder characterized by blepharophimosis, distinctive nose, hypoplastic maxilla, and skeletal abnormalities. Using homozygosity mapping in four VDEGS patients from three consanguineous families, Anastacio et al. [Anastacio et al. (2010); Am J Hum Genet 87:553-559] identified homozygous mutations in SCARF2, located at 22q11.2. Bedeschi et al. [2010] described a VDEGS patient with sclerocornea and cataracts with compound heterozygosity for the common 22q11.2 microdeletion and a hemizygous SCARF2 mutation. Because sclerocornea had been described in DiGeorge-velo-cardio-facial syndrome but not in VDEGS, they suggested that the ocular abnormalities were caused by the 22q11.2 microdeletion. We report on a 23-year-old male who presented with bilateral sclerocornea and the VDGEGS phenotype who was subsequently found to be homozygous for a 17 bp deletion in exon 4 of SCARF2. The occurrence of bilateral sclerocornea in our patient together with that of Bedeschi et al., suggests that the full VDEGS phenotype may include sclerocornea resulting from homozygosity or compound heterozygosity for loss of function variants in SCARF2.

}, keywords = {Abnormalities, Multiple, Adult, Arachnodactyly, Blepharophimosis, Bone and Bones, Chromosomes, Human, Pair 22, Contracture, Cornea, Corneal Diseases, Exons, Facies, Hand Deformities, Congenital, Homozygote, Humans, Male, Phenotype, Radiography, Scavenger Receptors, Class F, Sequence Analysis, DNA, Sequence Deletion, Young Adult}, issn = {1552-4833}, doi = {10.1002/ajmg.a.36425}, author = {Migliavacca, Michele P and Sobreira, Nara L M and Antonialli, Graziela P M and Oliveira, Mariana M and Melaragno, Maria Isabel S A and Casteels, Ingele and de Ravel, Thomy and Brunoni, Decio and Valle, David and Perez, Ana Beatriz A} }