Advances in the genetics of congenital ptosis

Congenital ptosis, a birth defects presents at birth or by 1 year of age, is characterized by the drooping of the upper eyelid. either in isolation (non-syndromic) or with many different systemic disorders (syndromic). The estimated prevalence of ptosis (congenital & acquired) ranges from 0.79 to 1.99 per 10,000 people in different populations, and it is more prevalent in males. The underlying pathogenesis of congenital ptosis are myogenic and neurogenic, related to the development of muscles and nerves. Although most cases are sporadic, there are familial transmission characteristics, including autosomal dominant, recessive mode and X-linkage inheritance patterns. Moreover, some forms are due to chromosomal aberrations and mutations and deletions in mitochondrial DNA. Genes involved in simple congenital ptosis are ZFHX4 and COL25A1. The clinical aspects of various syndromes involving congenital ptosis are partly caused by single gene mutations. However, the pathogenesis of congenital ptosis is not fully understood. We review the reported epidemiology, genetics and clinical features of congenital ptosis and associated syndromes here.

DLG3 Impairment Caused by Missense Variants in Non-Syndromic X-Linked Mental Retardation

X-lined intellectual disability (XLID), formerly known as X-lined mental retardation, is defined as genetically heterogeneous disorders with remarkable cognitive impairment and abnormal adaptive behaviour skills. This study demonstrates the Disc-large homolog 3 (DLG3) gene impairment in 2 different unrelated male probands. The results detected two missense mutations in the DLG3 gene, c.2267 G > A (p.Arg756Gln) and c.2359G > A p. (Gly787Ser) using by NGS. Both mutations were run in the PolyPhen2 program for mutation sensitivity check and showed to have 0.709 and 1, respectively. The familial transmission pattern of MR detected both mothers to be heterozygote. The mutations were shown to have caused non-syndromic XLMR (NS-XLMR) as both males did not show any abnormal facial or physiological features. Based on the IQ measurement, proband 1 and 2’ IQs were measured 40 and 33, and they were diagnosed with moderate and severe XLMR, respectively. Both affected males showed significant deterioration in neural development and behaviour abilities, which indicates the significant impact of the mutation on neurotransmitters and maintenance of NMDA receptors in neural functions. However, further molecular and functional studies are necessary to provide more conclusive evidence of the detailed abnormalities caused by the reported mutations.

'I Think it Highly Necessary to Have it Done Before They Go Out into the World': Inoculation, Responsibility and Patterns of Familial Transmission of Smallpox

This paper examines two research streams. First, it will discuss some contemporary familial perspectives on smallpox inoculation in the eighteenth century. This is followed by a look at the level of provision of the practice in Oxfordshire and some of its contiguous counties. Second, the paper will present some findings on the nature of the transmission of smallpox during local early eighteenth century epidemics in Banbury, Oxfordshire and Aynho, Northamptonshire. Finally, the paper will put forward some conclusions which encompass these two streams.