Unravelling the genetic basis of retinal dystrophies in Pakistani consanguineous families.

BACKGROUND: Retinitis Pigmentosa (RP) is a clinically and genetically progressive retinal dystrophy associated with severe visual impairments and sometimes blindness, the most common syndromic form of which is Usher syndrome (USH). This study aimed to further increase understanding of the spectrum of RP in the Khyber Pakhtunkhwa region of Pakistan. METHODOLOGY: Four consanguineous families of Pashtun ethnic group were investigated which were referred by the local collaborating ophthalmologists. In total 42 individuals in four families were recruited and investigated using whole exome and dideoxy sequencing. Among them, 20 were affected individuals including 6 in both family 1 and 2, 5 in family 3 and 3 in family 4. RESULT: Pathogenic gene variants were identified in all four families, including two in cone dystrophy and RP genes in the same family (PDE6C; c.480delG, p.Asn161ThrfsTer33 and TULP1; c.238 C > T, p.Gln80Ter) with double-homozygous individuals presenting with more severe disease. Other pathogenic variants were identified in MERTK (c.2194C > T, p.Arg732Ter), RHO (c.448G > A, p.Glu150Lys) associated with non-syndromic RP, and MYO7A (c.487G > A, p.Gly163Arg) associated with USH. In addition, the reported variants were of clinical significance as the PDE6C variant was detected novel, whereas TULP1, MERTK, and MYO7A variants were detected rare and first time found segregating with retinal dystrophies in Pakistani consanguineous families. CONCLUSIONS: This study increases knowledge of the genetic basis of retinal dystrophies in families from Pakistan providing information important for genetic testing and diagnostic provision particularly from the Khyber Pakhtunkhwa region.

Novel mutations in PDE6A and CDHR1 cause retinitis pigmentosa in Pakistani families.

AIM: To investigate the genetic basis of autosomal recessive retinitis pigmentosa (arRP) in two consanguineous/ endogamous Pakistani families. METHODS: Whole exome sequencing (WES) was performed on genomic DNA samples of patients with arRP to identify disease causing mutations. Sanger sequencing was performed to confirm familial segregation of identified mutations, and potential pathogenicity was determined by predictions of the mutations' functions. RESULTS: A novel homozygous frameshift mutation [NM_000440.2:c.1054delG, p. (Gln352Argfs*4); Chr5:g.149286886del (GRCh37)] in the PDE6A gene in an endogamous family and a novel homozygous splice site mutation [NM_033100.3:c.1168-1G>A, Chr10:g.85968484G>A (GRCh37)] in the CDHR1 gene in a consanguineous family were identified. The PDE6A variant p. (Gln352Argfs*4) was predicted to be deleterious or pathogenic, whilst the CDHR1 variant c.1168-1G>A was predicted to result in potential alteration of splicing. CONCLUSION: This study expands the spectrum of genetic variants for arRP in Pakistani families.

Outcome of open transcortical approach in the management of intraventricular lesions.

OBJECTIVE: To evaluate the outcome of management of intraventricular lesions operated by an open transcortical (nonendoscopic) approach. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of Neurosurgery, Dow University of Health Sciences and Civil Hospital, Karachi, from January 2009 to December 2011, with six months follow-up. METHODOLOGY: All cases with lesions in the lateral ventricle and anterior third ventricle operated by open transcortical approach, were included after informed consent. Total excision of the lesion was attempted in all cases. Patients were analyzed for outcome in terms of establishment of diagnosis, completeness of resection, morbidity and mortality. RESULTS: A total of 33 patients were operated. Twenty three were males and 10 were females. Colloid cyst was diagnosed in 14 patients (42%), giant cell astrocytoma and choroid plexus papilloma in 4 cases each and subependymoma and central neurocytoma in 2 cases each, epidermoid, choroid plexus carcinoma, oligodendroglioma, metastasis, meningioma, ependymoma and cavernous hemangioma in one patient each. The overall outcome could be labeled as good in 24 out of 33 cases (73%) and in 8 cases (24%) it was fair. One patient died due to ventriculitis and was categorized as poor outcome (3%). Postoperative complications included meningitis, seizures, intraventicular haemorrhage, subdural collection and transient hemiparesis. Nine patients had persistent hydrocephalus requiring ventriculoperitoneal shunt. CONCLUSION: Conventional open transcortical approach is still effective in getting conclusive biopsy or near total excision of the lesion with minimum morbidity.

Intramedullary spinal tuberculoma.

Spinal intradural intramedullary tuberculoma is extremely rare entity of tuberculosis involving the nervous system. Because of its atypical symptomatology, it must be considered in differential diagnosis of spinal cord lesions, especially where prevalence of tuberculosis is high. In this case report this atypical disease is described where good outcome was achieved by surgical excision of the intramedullary lesion followed by antituberculous therapy.