Clinical and Mutation Spectra of Cockayne Syndrome in India.

BACKGROUND: Cockayne syndrome is an autosomal recessive disorder caused by biallelic mutations in ERCC6 or ERCC8 genes. AIMS: To study the clinical and mutation spectrum of Cockayne syndrome. SETTING AND DESIGN: Medical Genetics Outpatient Department of Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow. This was a prospective study from 2007 to 2015. MATERIALS AND METHODS: Clinical details were recorded, and sequencing of ERCC6 and ERCC8 were performed. RESULTS AND CONCLUSIONS: Of the six families, one family had a homozygous mutation in ERCC8 and the other five families had homozygous mutations in ERCC6. Novel variants in ERCC6 were identified in four families. Phenotypic features may vary from severe to mild, and a strong clinical suspicion is needed for diagnosis during infancy or early childhood. Hence, molecular diagnosis is needed for confirmation of diagnosis in a child with a suspicion of Cockayne syndrome. Prenatal diagnosis can be provided only if molecular diagnosis is established in the proband.

Phenotypic characterization of derivative 22 syndrome: case series and review.

Emanuel syndrome is caused due to an additional derivative chromosome 22 and is characterized by severe intellectual disability, microcephaly, failure to thrive, preauricular tags or pits, ear anomalies, cleft or high-arched palate, micrognathia, kidney abnormalities, congenital heart defects and genital abnormalities in males. In 99% of the cases, one of the parents is a carrier of balanced translocation between chromosomes 11 and 22. It occurs due to malsegregation of the gametes with 3:1 segregation. In this case series, we describe four patients with diverse manifestations of this condition. The craniosynostosis observed in one case is a novel finding which has never been reported previously. This study aims to widen the phenotypic spectrum of Emanuel syndrome and provide cytogenetic microarray based breakpoints in two of the cases, thus supporting close clustering of the breakpoints of this common recurrent chromosomal rearrangement.

Double Segment Chromosomal Imbalance due to Inherited Chromosomal Translocation: Detection by Cytogenetic Microarray.

BACKGROUND: Balanced translocations are common with the incidence of 1 in 500. CASE CHARACTERISTICS: Two cousins with intellectual disability with family history of holoprosencephaly. RESULTS: Microarray showed gain on chromosome 7 and loss on chromosome 11 and vice versa in the other cousin. CONCLUSION: We highlight the importance of detailed family history, pedigree analysis, and utility of microarray.

Novel mutations in the transmembrane natriuretic peptide receptor NPR-B gene in four Indian families with acromesomelic dysplasia, type Maroteaux.

Acromesomelic dysplasia, type Maroteaux is a disorder characterized by disproportionate short stature predominantly affecting the middle and distal segments of the upper and lower limbs. It is an autosomal recessive disorder due to mutation in NPR2 gene which impairs skeletal growth. To screen the mutations in the gene NPR2, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected individuals of four families and sequenced. Four homozygous mutations in four different families were identified. These include three novel mutations including a deletion frameshift mutation (p.Cys586Ter), one nonsense mutation (p.Arg479Ter), one missense mutation (p.Val187Asp) and one reported missense mutation (p.Tyr338Cys). The study describes phenotypes of Indian patients and expands the mutation spectrum of the disorder.

Genetic Approach to Diagnosis of Intellectual Disability.

Intellectual disability is a non-specific phenotype present in a genetically heterogeneous group of disorders. It is characterized by deficits in intellectual and adaptive functioning, presenting before 18 y of age. Identifying the cause of ID is important to provide treatment where available, genetic counseling, recurrence risks and reproductive options for subsequent pregnancies. Advances in technology, especially next generation sequencing and microarrays, have greatly increased the diagnostic yield of evaluation in cases of ID. This paper describes the points in history taking and examination in the evaluation of a proband, and discusses the proper use of newer diagnostic technologies.

Knowledge of Cord Blood Banking in General Population and Doctors: A Questionnaire Based Survey.

OBJECTIVES: To assess the knowledge of the general population and the medical specialists about the purpose and utility of cord blood banking. METHODS: One hundred individuals from the general population and 100 clinicians from various departments were enrolled in the study between August 2013 and November 2013. RESULTS: Fifty eight percent of the doctors and 82 % of the lay persons did not know any indication or were not aware of the correct indications of the use of cord blood for transplantation. Around half of the lay persons (42 %) and doctors (37 %) thought that umbilical cord blood can be used to treat any genetic disorder including Duchenne muscular dystrophy and mental retardation. Nineteen percent of the doctors thought that umbilical cord blood can be used to treat thalassemia in the same child. CONCLUSIONS: The propaganda done by cord blood banks that cord blood is a biological insurance for the child is misleading and should be discouraged. The obstetricians and the pediatricians should take a central role in providing the correct information to would be parents to help them in taking a correct decision.

White matter changes in GM1 gangliosidosis.

BACKGROUND: GM1 gangliosidosis is a disorder due to GLB1 gene mutation. CASE CHARACTERISTICS: A 4-yr-old boy with neuroregression and optic atrophy with periventricular hyperintensity on magnetic resonance imaging. OUTCOME: Beta galactosidase enzyme activity was low which was confirmed by GLB1 sequencing. MESSAGE: We highlight the white matter changes in late infantile GM1 gangliosidosis.

Polymorphisms in MTHFR, MTHFD, and PAI-1 and recurrent miscarriage among North Indian women.

PURPOSE: The aim of this study was to investigate the association between MTHFR C677T, A1298C, MTHFD G1958A and plasminogen activator inhibitor type 1 (PAI-1) 4G/5G polymorphism among first trimester recurrent miscarriages. MATERIALS AND METHODS: DNA was extracted from peripheral blood samples from 200 patients and 300 controls. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and sequencing were used to identify the polymorphisms. We have analyzed the frequencies, odds ratio, Hardy-Weinberg equilibrium. RESULTS: MTHFR C677T, A1298C, and MTHFD G1958A variant alleles were found to be significantly more prevalent in patients than control. However, variant genotype of MTHFR C677T (OR = 2.54; 95 % CI = 1.23-5.24; p value = 0.014), 1298C (OR = 2.23; 95 % CI = 1.09-4.52; p value = 0.028), and MTHFD-1958 showed significant association with pregnancy loss (OR = 2.36; 95 % CI = 1.39-4.02; p value = 0.002). Both MTHFR 677 and MTHFD 1958 showed susceptible effect under recessive model of inheritance. PAI-1 mutations showed no significance. CONCLUSION: We observed significant susceptible effects of MTHFR C677T, A1298C, and MTHFD G1958A among RM cases. Our data points toward the multifactorial nature of the recurrent miscarriage as relative contribution of variant genotype of MTHFR C677T is only twofold and further decreased to only onefold, and MTHFD-1958 lost its significance upon meta-analysis.