Detection of steroid sulfatase gene deletion [STS] in Egyptian males with X-linked ichthyosis

Ichthyosis is a disorder of keratinization characterized by diffuse uniform and persistent scales resulting from abnormal epidermal differentiation or metabolism. Ichthyosiform dermatoses are classified into four major types, ichthyosis vulgaris, X-Linked ichthyosis, congenital recessive ichthyosis and lastly epidermolytic hypekeratosis which was previously called bullous ichthyosiform erythroderma. The identification of steroid sulfatase as the cause of X-Linked ichthyosis points to the importance of this enzyme in skin desquamation. Fluorescent in situ hybridization [FISH] analysis is a good diagnostic technique to detect a common deletion of the STS gene. Most patients with X-Linked ichthyosis have large deletions of the STS locus in this study, we aimed to detect the X-Linked type of ichthyosis, diagnosed by detection of STS gene deletions among Egyptian males. We performed this study on Egyptian males complaining of X-linked ichthyosis who were subjected to clinical examination, pedigree analysis of the family, cytogenetic studies using G-banding technique and fluorescent in situ hybridization [FISH] using locus specific probe for stereoid sulfatase [STS] gene which is located at chromosome Xp22.3. Our results showed that 11.11% of patients had nocturnal enuresis and 33.33% showed STS gene deletion by FISH study. The current study underlines the difficulty of diagnosis of X-Linked ichthyosis on the clinical features or pedigree analysis of the family in Egypt and the importance of cytogenetic and molecular cytogenetic studies for diagnosis. Fluorescent in situ hybridization [FISH] technique is a good, reliable, and rapid diagnostic tool to detect STS gene deletion. Since FISH will not detect partial deletion or point mutations, we recommended further molecular studies to reach the proper diagnosis of X-linked ichthyosis

Maternal balanced translocation [4;21] leading to an offspring with partial duplication of 4q and 21 q without phenotypic manifestations of down syndrome

We describe an 8-year old female with supernumerary chromosome der[21]t[4;21][q25;q22] resulting in partial trisomy 4q25-qter and partial trisomy 21[pter-q22]. The extra material was originated from a reciprocal balanced translocation carrier mother [4q;21q]. Karyotyping was confirmed by FISH using whole chromosome painting probes for 4 and 21q and using 21q22.13-q22.2 specific probe to rule out trisomy of Down syndrome critical region. Phenotypic and cytogenetic findings were compared with previously published cases of partial trisomy 4q and 21 q. Our patient had the major criteria of distal trisomy 4q namely severe psychomotor retardation, growth retardation, microcephaly, hearing impairment, specific facies [broad nasal root, hypertelorism, ptosis, narrow palpebral fissures, long eye lashes, long philtrum, carp like mouth and malformed ears] and thumbs and minor feet anomalies. In spite of detection of most of the 3 copies of chromosome 21, specific features of Down syndrome [DS] were lacked in this patient, except for notable bilateral symmetrical calcification of basal ganglia. This report represents further delineation of the phenotype-genotype correlation of trisomy 4q syndrome. It also supports that DS phenotype is closely linked to 21q22. Nevertheless, presence of basal ganglia calcification in this patient may point out to a more proximal region contributing in its development in DS, or that genes outside the critical region may influence or control manifestations of DS features

Phenotypic characterization of chromosome 22 rearrangement

Chromosomal rearrangement can lead to altered gene dosage, resulting in genomic disorder. Most of chromosomal rearrangements are associated with congenital malformations and mental retardation. Therefore genomic disorders have a large impact on human health. The present study focus on chromosome 22 as a model for chromosomal rearrangement, because of its susceptibility to genomic instability. We aim to describe and clarify the associated phenotypic changes of patients with chromosome 22 rearrangement using data of our patients and others of literature. We attempt to identify the role of various 22q regions in human development and phenotype. The present study included 8 patients. They were selected among patients referred to the Clinical Genetics Department, NRC. They were representing different numerical and structural chromosome 22 rearrangements. Thorough clinical, cytogenetic and FISH studies were provided. The phenotypic manifestations were analyzed and evaluated according to the specific rearrangement. The 22q13 deletion was represented by 2 patients, displaying ring 22 and simple deletion. We observed that overall developmental delay, severe impairment of language, microcephaly, convulsions and or EEG changes were the overlapping findings among the two patients. More severe phenotypic manifestation were exhibited by patient of simple deletion, which could be the consequence of large deletion. Patient of ring 22 exhibited multiple. caf‚ au lait spots, sensorineural hearing loss and brain cyst which are consistent findings in NF2 [MIM 114570]. Disruption of NF2 gene at 22q11.21-q13.1 was highly suggestive in our patients of 22q13 deletion. Patients of NF2 should be investigated for chromosome 22q simple or cryptic deletion. Partial trisomy of chromosome 22 resulting from an interstitial duplication of 22q11.2 was represented by a patient. She exhibited cat eye syndrome [CES] phenotype [MIM 115470]. It strengthens the suggestion that trisomy of cat eye critical region [CECR] [22q11.2] is sufficient to cause CES with variable clinical findings. Paracentric inversion [PAI] of chromosome 22 was represented by 4 patients, two of them were sibs. PAI was paternally inherited, 3 patients carried the identical inversion of the phenotypically normal fathers. Non identical inversion was disclosed in one of both sibs. He exhibited congenital heart disease, one of his breakpoints was involved in 22q11.2 region. Deletion of 22q11.2 region had not been detected by conventional FISH studies in our patient. It might be explained by a small deletion that had not been detected by routine FISH studies resulting from unbalanced molecular recombinant from unequal crossing over in the inverted sequence. Further molecular studies may facilitate the identification of genes involved in cardiac morphogenesis. Unexplained mental retardation/delayed motor and mental development, abnormal facies, convulsions/EEG changes and hearing defects could be attributed to missed chromosome 22 rearrangement, particularly PAI. Our ascertainment of 7 cases with different chromosome 22 rearrangement, we observed that abnormal ear development and or hearing deficiency was a constant and common clinical finding among our patients. In general, chromosome 22 may play an important role in ear and hearing development in human. In particular, genomic disorder of 22q11.2 region has a major role in cardiac morphogenesis and CES phenotypes

Genetic studies of congenital contractures of limbs

Congenital contractures of limbs comprise a category of limb malformations that poses a difficult diagnostic and therapeutic problem. They can occur as an isolated defect or as part of syndromes. This study included 46 patients with congenital contractures of limbs. Cases were referred to the Limb and Skeletal Anomaly Clinic at the National Research Centre. Detailed family history, pedigree construction, physical and orodental examination, anthropometric measurements and radiological studies were carried out for all cases. Cytogenetic analysis using G-banding and high resolution techniques were carried out for 36 cases. Biochemical and neurophysiologic studies were conducted for selected cases. According to clinical phenol-type, cases were classified into 4 main categories, which were further subdivided into 16 entities. Category [I]: included congenital contractures that affected primarily the musculoskeletal system, 18 cases were in this category comprising 8 entities. Category [II]: Twenty cases had musculoskeletal involvement in addition to other system malformations or anomalies comprising 5 entities, of which 11 cases had multiple pterygium syndrome. Category [III]: Six patients in this study had musculoskeletal involvement plus lethality, CNS anomalies or mental retardation. Four were diagnosed as Pena-Shokeir syndrome, one with Aase-Smith syndrome and another case showed dup [1] [p36.1-36.2]. Category [IV]: Contracture deformities of limbs due to environmental factors, which were present in 2 cases only. Detailed genetic and clinical analysis of different cases with congenital contractures of limbs are presented in this study. Our work proved that contracture deformities of limbs due to genetic causes were the most common [44 cases], while those related to environmental causes were only present in 2 cases. This emphasizes the importance of careful clinical examination and categorization o patients with congenital contracture! of limbs and the necessity of proper genetic counseling of affected families. The study of the molecular causes of these disorders is important for the understanding of the pathogenesis hoping for their prevention, early intervention and gene therapy