Search results for "Pedigree"

Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome.

2007

Peters, T.A./0000-0001-8443-5500; van Beersum, Sylvia E.C./0000-0002-4552-2908; Cremers, Frans/0000-0002-4954-5592; Roepman, Ronald/0000-0002-5178-8163 WOS: 000247619800019 PubMed: 17558407 Protein- protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis ( NPHP), Leber congenital amaurosis, Senior- Loken syndrome ( SLSN) or Joubert syndrome ( JBTS)(1-6). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1- like protein ( RPGRIP1L) is a homolog of RPGRIP1 ( RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis(7,8). We show t…

Rare NLRP12 variants associated with the NLRP12-autoinflammatory disorder phenotype: an Italian case series.

2013

Four unrelated patients with lubs X-linked mental retardation syndrome and different Xq28 duplications

2010

The Lubs X-linked mental retardation syndrome (MRXSL) is caused by small interstitial duplications at distal Xq28 including the MECP2 gene. Here we report on four novel male patients with MRXSL and different Xq28 duplications delineated by microarray-based chromosome analysis. All mothers were healthy carriers of the duplications. Consistent with an earlier report [Bauters et al. (2008); Genome Res 18: 847-858], the distal breakpoints of all four Xq28 duplications were located in regions containing low-copy repeats (LCRs; J, K, and L groups), which may facilitate chromosome breakage and reunion events. The proximal breakpoint regions did not contain known LCRs. Interestingly, we identified …

Editor's Note: Relates to: ‘Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to p…

2020

Aims The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD). Methods and results Of the theoretical estimated prevalence of 1/500 for heterozygous FH, <1% are diagnosed in most countries. Recently, direct screening in a Northern European general population diagnosed approximately 1/200 with heterozygous FH. All reported studies document failure to achieve recommended LDL cholesterol targets in a large proportion of individuals with FH, and up to 13-fold increased risk of CHD. Based on prevalen…

Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis.

2010

Hajdu-Cheney syndrome is a rare autosomal dominant skeletal disorder with facial anomalies, osteoporosis and acro-osteolysis. We sequenced the exomes of six unrelated individuals with this syndrome and identified heterozygous nonsense and frameshift mutations in NOTCH2 in five of them. All mutations cluster to the last coding exon of the gene, suggesting that the mutant mRNA products escape nonsense-mediated decay and that the resulting truncated NOTCH2 proteins act in a gain-of-function manner.

Characterization of non-expressed C4 genes in a case of complete C4 deficiency: identification of a novel point mutation leading to a premature stop …

1998

The genetic basis of complete C4 deficiency in a patient with SLE was investigated. Previous studies have demonstrated that this patient has two different major histocompatibility complex (MHC) haplotypes that each contain a major deletion and a non-expressed C4 gene. In the present study, non-expression of the C4 genes was explained by the finding of two distinct C4 gene mutations. A previously described two base pair insertion in exon 29 of the C4 gene was detected in the paternal MHC haplotype [HLA-A2, B40, SC00, DR6]. The maternal haplotype [HLA-A30, B18, F1C00, DR3] carried a C4 gene with a one base pair deletion in exon 20 generating a premature stop codon. This mutation was neither f…

Antibody Response to Meningococcal Polysaccharides A and C in Patients with Complement Defects

1993

Patients with defects of terminal complement components are particularly exposed to the risk of developing neisserial infections and seem to respond poorly to meningococcal capsular polysaccharide (PS) C via natural immunization. The sole meningococcal PSC is. on the other hand, an excellent immunogen in normal people. Considering the great importance of vaccine prophylaxis for the prevention of meningococcal infections in patients with complement defects, it is crucial to study the antibody response to the sole meningococcal PS in these patients. We therefore analysed the levels of anti-PSA and PSC antibodies in the members of four families including patients with homozygous and heterozygo…

KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome

2015

Background Joubert syndrome (JBTS) and related disorders are defined by cerebellar malformation (molar tooth sign), together with neurological symptoms of variable expressivity. The ciliary basis of Joubert syndrome related disorders frequently extends the phenotype to tissues such as the eye, kidney, skeleton and craniofacial structures. Results Using autozygome and exome analyses, we identified a null mutation in KIAA0556 in a multiplex consanguineous family with hallmark features of mild Joubert syndrome. Patient-derived fibroblasts displayed reduced ciliogenesis potential and abnormally elongated cilia. Investigation of disease pathophysiology revealed that Kiaa0556-/- null mice possess…

New syndrome: Autosomal dominant microcephaly and radio-ulnar synostosis

1994

To date, the combination of microcephaly and radio-ulnar synostosis has not been recognized as a distinct clinical and genetic entity. We report on 4 familial cases with this previously undescribed combination of defects, showing autosomal dominant inheritance (Fig. 1). © 1994 Wiley-Liss, Inc.

A two base pair deletion in the PQBP1 gene is associated with microphthalmia, microcephaly, and mental retardation.

2007

X-linked mental retardation has been traditionally divided into syndromic (S-XLMR) and non-syndromic forms (NS-XLMR), although the borderlines between these phenotypes begin to vanish and mutations in a single gene, for example PQBP1, can cause S-XLMR as well as NS-XLMR. Here, we report two maternal cousins with an apparently X-linked phenotype of mental retardation (MR), microphthalmia, choroid coloboma, microcephaly, renal hypoplasia, and spastic paraplegia. By multipoint linkage analysis with markers spanning the entire X-chromosome we mapped the disease locus to a 28-Mb interval between Xp11.4 and Xq12, including the BCOR gene. A missense mutation in BCOR was described in a family with …