The study of human hereditary disorders was carried out in patients from Civil Hospital Karachi. Liaquat University of Medical and Health Sciences (LUMHS). Jamshoro. and Civil Hospital Nausheroferoz. Sindh Pakistan.
The genetic disorders were Schizophrenia. Albinism. Down's syndrome, polydactyl and syndyctly, and neurofibromatosis type 1, neurofibromatosis type 5, and neurofibromatosis type 6. In Pakistan the literature shows that no work has been done on neurofibromatosis. This was the main reason giving much emphasis on neurofibromatosis. Detailed study showed different types of neurofibromatosis. with different modes of expression. Large pedigrees of NF1 were also recorded, with their detailed history. Though the disease is not contagious. but it leaves very negative and depressive impact on the subject and the family. It is seen that NF1 flourish and become aggressive with the progression of age, and become more complicated in poverty.
In this study 96 cases (ninety-six) each confirmed by using NIH consensus criteria. The patients were from different areas of Sindh, Pakistan. In six familial cases two to three members were affected with NF1. In one family (largest family) nine NF1 individuals were seen in three generations. both male and female were affected almost in equal ratio, with out any discrimination of gender. In other two families individuals were affected with both Plexiform and NF1 In another two families three members were affected with NF1. Three more families studied which included two members affected by NF1 in two generations.
Present study includes seven different types of Plexiform: Plexiform of ann. Plexiform of eye. Plexiform of leg. Plexiform of ankle, Plexiform of thigh, Plexiform of scalp. and Plexiform of mandible. The youngest subject with Plexiform of eye was a four year boy. Four NF1 cases were on follow up study.
The study also include two very rare types of neurofibromatosis which occur world wide, named as NF5, that shows bilateral neurofibromatosis , and type NF6, that shows very large size cafe-au-lait macules, and it covers more or less complete back of the subject. with neurolibroma. Biopsies of large tumors were performed in all patients. Lisch- nodules were identified positive in 59% subjects. Many subjects were severely affected, having other signs of NF1.
Other types of hereditary disorders were also studied, i.e. schizophrenia_ with a large pedigree of six generations having five subjects with well developed schizophrenic symptoms. Polydactyly: the pedigree shows eight affected individuals, (six females and two males) in four generations. Albinism: it was present in four generation, seven subjects were affected, (four females and three males). Down's syndrome. the pedigree comprises of four generations. having six affected members. three male and three female.
The molecular biology approach for the study of NF I- genomic disorder, carried out through PCR-technique. The primers used in this study were based on the previously described deletion mutation spectrum by Lujiten et al (2001) they observed that at the exon 28 there was a four base pair deletion which resulted in NF I disease. In order to screen mutation at the same position, in our population. the primer E28-4913 was used for detection of four base pair deletion. The results indicated that this particular deletion is not present in our population, therefore the occurrence of NF1 disease is not because of four base pair deletion. It may be the result of four base pair deletion at some other position in the neurofibroma gene.
Neurofibromatosis type 1 (NF1). is a neural crest origin autosomal dominant disorder. The morbid gene is located on chromosome 17q 11.2. The major phenotype feature of the disease is the widespread occurrence of benign dermal tumors or neurofibroma, and plexiform neurofibroma. Neurofibromatosis type 1 affects 1 in 4000 individuals. and is characterized with variable clinical presentation. The NF1 gene spans at 350 kb on long amt chromosome 17 with 60 exons. The gene exhibits high mutation rate and about 59 % are sporadic new mutations.