| 1. |
- Nawaz, Sadia, et al.
(författare)
-
Non-bullous congentital ichthyosiform erythroderma associated with homozygosity for a novel missense mutation in an ATP binding domain of ABCA12
- 2012
-
Ingår i: EJD. European journal of dermatology. - : John Libbey Eurotext. - 1167-1122 .- 1952-4013. ; 22:2, s. 178-181
-
Tidskriftsartikel (refereegranskat)abstract
- A Mutations in the gene encoding the ABCA12 protein are associated with different subtypes of autosomal recessive congenital ichthyosis (ARCI), including Harlequin ichthyosis (HI), lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE). Disruption of ABCA12 lead to perturbed lipid transport in lamellar granules and a defective intercellular lipid layer of the stratum corneum. We have identified a large consanguineous Pakistani family affected by NCIE. Autozygosity mapping showed that affected individuals are homozygous for the ABCA12 gene region. Subsequent mutation screening revealed a homozygous c.4676G>T transition in all five affected family members. The mutation results in a novel p.G1559V substitution within the first nucleotide binding domain of ABCA12. The combined results support that an ABCA12 missense mutation, despite its location in a functional domain, may be associated with a mild ichthyosis phenotype. Furthermore, our findings increase the mutational spectrum in ABCA12 associated with ARCI of diagnostic and prognostic importance.
|
|
| 2. |
- Nawaz, Sadia, et al.
(författare)
-
Report of a recurrent mutation in ARS (component B) gene with severe Mal de Meleda in a large consanguineous Pakistani family
- 2011
-
Ingår i: Pakistan journal of medical sciences print. - 1682-024X .- 1681-715X. ; 27:3, s. 686-689
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To characterize the disease causing mutation in a large consanguineous Pakistani family with severe Mat de Meleda (MDM) or keratosis palmoplantaris transgrediens, a rare autosomal recessive skin disorder. Methodology: Single nucleotide polymorphism (SNPs) genotyping was performed using the Gene Chip Mapping 250K array (Affymetrix). Homozygosity mapping and sorting of genomic regions were performed with dedicated software called AutoSNPa. Selected regions were further investigated by genotyping with microsatellite markers derived from known and novel pOlymorphic repeats. Two-point LOD score calculation was performed by using the MLINK of Fast link computer package. All three coding exons of ARS (component B) gene were amplified by PCR and sequenced. Conclusion: Sequencing of all the coding exons of ARS (component B) gene in the affected individuals revealed a recurrent missense mutation in exon 3 at base pair 256 from Guanine to Alanine (256G>A) and as a result the amino acid Glycine is replaced by Arginine at position 86 (G86R). This finding will facilitate control of affected MDM births in the Pakistani families.
|
|
| 3. |
- Rasool, Mahmood, et al.
(författare)
-
A novel missense mutation in the EDA gene associated with X-linked recessive isolated hypodontia
- 2008
-
Ingår i: Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1434-5161 .- 1435-232X. ; 53:10, s. 894-8
-
Tidskriftsartikel (refereegranskat)abstract
- Isolated hypodontia, or congenital absence of one to six permanent teeth (OMIM 300606), is a common condition that affects about 20% of individuals worldwide. We identified two extended Pakistani pedigrees segregating X-linked hypodontia with variable expressivity. Affected males show no other associated anomalies, and obligate carrier females have normal dentition. We analyzed the families with polymorphic markers in the ectodysplasin A (EDA) gene region and obtained significant linkage to the phenotype in each pedigree (Z(max) 3.29 and 2.65, respectively, at theta = 0.00). Sequence analysis of the coding regions of EDA revealed a novel missense mutation c.1091T>C resulting in a methionine to threonine substitution (p.M364T) in the tumor necrosis factor (TNF) homology domain. Met364 is a highly conserved residue located on the outer surface of the EDA protein. From our findings, we suggest that the mutation disturbs but does not destroy the EDA structure, resulting in the partial and unusually mild ED phenotype restricted to hypodontia.
|
|
| 4. |
- Zakaria, Muhammad, et al.
(författare)
-
Primary microcephaly, primordial dwarfism, and brachydactyly in adult cases with biallelic skipping of RTTN exon 42
- 2019
-
Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 40:7, s. 899-903
-
Tidskriftsartikel (refereegranskat)abstract
- Biallelic and pathogenic variants in the RTTN gene, encoding the centrosomal protein Rotatin, are associated with variable degrees of neurodevelopmental abnormalities, microcephaly, and extracranial malformations. To date, no reported case has reached their third decade. Herein, we report on a consanguineous family with three adult members, age 43, 57, and 60 years respectively, with primary microcephaly, developmental delay, primordial dwarfism, and brachydactyly segregating a homozygous splice site variant NM_173630.3:c.5648–5T>A in RTTN. The variant RTTN allele results in a nonhypomorphic skipping of exon 42 and a frameshift [(NP_775901.3:p.Ala1883Glyfs*6)]. Brain MRI of one affected individual showed markedly reduced volume of cerebral lobes and enlarged sulci but without signs of neural migration defects. Our assessment of three adult cases with a biallelic RTTN variant shows that a predicted shortened Rotatin, lacking the C‐terminal end, are associated with stationary clinical features into the seventh decade. Furthermore, our report adds brachydactyly to the phenotypic spectrum in this pleiotropic entity.
|
|
