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Disorders of bone and connective tissue
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Many causes of a short neck find their way into this category but Klippel-Feil syndrome remains heterogeneous even after their removal. Key clinical features (not all required) are a short neck, low posterior hairline and restriction of neck movement, and there is usually some fusion of cervical vertebrae on X-ray. Where the case is an isolated one, the risk for sibs is probably low, although minor degrees of cervical vertebral fusion may be more frequent in relatives, and autosomal recessive families have been reported. The risk for children is significant since some cases are dominantly inherited; no precise figure exists. Familial mutations have been recognised in a number of genes (such as GDF6) but most cases are sporadic. Congenital heart disease is a common accompaniment in patients. The specific association with severe deafness and Duane anomaly (Wildervanck syndrome) is more common in girls. Cases with urogenital abnormalities may have the müllerian, renal, cervicothoracic somite abnormalities (MURCS) association. Careful clinical assessment and full skeletal survey should allow future delineation of specific entities within this group.
Molecular genetics with clinical characteristics of Leber congenital amaurosis in the Han population of western China
Published in Ophthalmic Genetics, 2021
Luyao Zhu, Wangbin Ouyang, Minfang Zhang, Hao Wang, Shiying Li, Xiaohong Meng, Zheng Qin Yin
LCA is highly genetically heterogeneous and is mostly inherited in an autosomal recessive manner, yet there can be some exceptions. So far, mutations in 25 genes have been contributive to LCA; their details are available at RetNet (https://sph.uth.edu/Retnet/), an internationally authentic website revealing related genes causing retinal dystrophies. The genes are expressed solely or predominantly in various functional pathways in the retina or the retinal pigment epithelium (RPE). Examples include those involved in guanine synthesis (IMPDH1), photoreceptor morphogenesis (CRB1, CRX, and GDF6), ciliary transport process (CEP290, CLUAP1, IFT140, IQCB1, LCA5, RPGRIP1, SPATA7, and TULP1), photo-transduction (AIPL1, GUCY2D, and RD3), and retinoid cycle (LRAT, RDH12, and RPE65) (2). Additionally, a previous study has demonstrated that the widespread range of the mutation spectrum varies remarkably among different populations (3). Nevertheless, a substantial proportion of patients (10%–20%) remains undetected despite a variety of molecular testing tools (5–7).
Novel causative variants in patients with achromatopsia
Published in Ophthalmic Genetics, 2018
Ehab Abdelkader, Oliver Brandau, Carsten Bergmann, Nuha AlSalamah, Sawsan Nowilaty, Patrik Schatz
NGS panel analysis included in all cases the core genes for ACHM, CNGA3, CNGB3, GNAT2, and PDE6C. In cases 2, 3, and 5, the analysis included additional genes for cone, cone/rod, or macular degeneration (ABCA4, ACBD5, ADAM9, AIPL1, BEST1, C1QTNF5, C21orf2, C8orf37, CABP4, CACNA2D4, CDH3, CDHR1, CERKL, CNNM4, CRX, ELOVL4, FBLN5, GUCA1A, GUCA1B, GUCY2D, HMCN1, ITM2B, KCNV2, MERTK, PITPNM3, PROM1, PRPH2, RAB28, RAX2, RDH5, RGS9, RGS9BP, RIMS1, RP1L1, and RPGR with exclusion of ORF15, RPGRIP1, SEMA4A, TEAD1, TIMP3, UNC119, and WASF3). For patient 7, the NGS panel analysis included as well genes for Leber’s congenital amaurosis (LCA; ADAMTS18, AIPL1, ALMS1, CABP4, CEP290, CRB1, CRX, DHX38, DTHD1, GDF6, GUCY2D, IMPDH1, IQCB1, KCNJ13, LCA5, LRAT, MERTK, MPDZ, MYO7A, NMNAT1, OTX2, RD3, RDH12, RPE65, RPGRIP1, SPATA7, and TULP1) and autosomal recessive retinitis pigmentosa (arRP; ABCA4, ACACB, ARL6, BBS2, BEST1, C2ORF71, C8ORF37, CERKL, CLRN1,CNGA1, CNGB1, CRB1, CYP4V2, DHDDS, DHX38, EMC, EYS, FAM161A, FLVCR1, GNPTG, GPR125, GRID2, IDH3B, IMPG2, KIAA1549, LRAT, MAK, MERTK, MPDZ, MTTP, MVK, NEK2, NR2E3, NRL, PDE6A, PDE6B, PDE6G, PLA2G5, PRCD, PROM1, PRPH2, RBP3, RBP4, RDH12, RDH5, RERG, RGR, RHBDD2, RHO, RLBP1, RP1, RPE65, SAG, SPATA7, TTC8, TPPA, and TULP1). Reference sequences used variant nomenclature are NM_006204.3 for PDE6C and NM_001298.2 for CNGA3.
Congenital stationary night blindness associated with morning glory disc malformation: a novel hemizygous mutation in CACNA1F
Published in Ophthalmic Genetics, 2018
Ehab Abdelkader, Sara AlHilali, Christine Neuhaus, Carsten Bergmann, Tahani AlMurshed, Patrik Schatz
Molecular genetic testing was done for the patient using next-generation sequencing (NGS, Illumina HiSeq 1500, performed by Center for Human Genetics, Bioscientia, Ingelheim, Germany) of the known genes involved in rod–cone dystrophy, cone–rod dystrophy, macular dystrophy, and cone dystrophy comprising 715 exons of 45 genes. Testing for the microphthamia panel was also conducted (GDF3, GDF6, MAF, OTX2, SHH, and VSX2) (8–11): The resulting sequence data for the CACNA1F gene (OMIM 300110; Locus: Chromosome Xp11.23) were compared to the reference sequence NM_005183.3 and for the RGS9BP gene (OMIM 607814; Locus Chromosome 19q13.11) to the reference sequence NM_207391.2. Direct sequencing of CACNA1F was performed for both parents. NGS revealed a hemizygous missense variant c.3401G>A (p.Gly1134Asp) in exon 28 of CACNA1F in the 7 year old boy. His mother was found to be a heterozygous carrier of the same variant, whereas the father did not carry any mutations in CACNA1F.