Bloom's syndrome–‐a first report from India

Abstract

A 6‐year‐old boy presented with complaints of redness and scarring over the face to the outpatient clinic of the Dermatology Department of Maulana Azad Medical College and Lok Nayak Hospital, New Delhi, India. The child was apparently normal until the age of 6 months when his mother noticed an erythematous eruption with small blisters and mild discomfort over the face on exposure to sunlight. Gradually, the eruption became more progressive, extending to the forehead, nose, and ears with the development of oozing, crusting, atrophy, and telangiectasias over the face, despite treatment. Over the last 3 months, he had developed ulceration of the skin over the right cheek just below the lower eyelid without any signs of healing. No history suggestive of constitutional symptoms, bowel and bladder complaints, Raynaud's phenomenon, alopecia, discoloration of urine on standing, and chronic systemic or cutaneous infections could be obtained. The patient is a product of a full‐term pregnancy with normal vaginal delivery of nonconsanguineous parents. His developmental milestones were delayed, with sitting at 2.5 years and standing and speech at 3 years. Our patient is a Hindu by religion and Rajput by caste. India is a vast land mass, bounded by the Himalayan mountains to the north‐west, lush green forests to the east, and the scenic Kashmir valley to the north; the land tapers into the Indian Ocean at the southern peninsula where the Bay of Bengal and Arabian Sea meet. India is a republic consisting of different states and union‐territories with Christians, Hindus, Muslims, Sikhs, and people from other religions. Among the Hindus, several castes exist, such as ‘‘Brahmins,’' ‘‘Kshatriyas’' (Rajputs–‐the warrior clan), ‘‘Vaishyas,’' and ‘‘Shudras,’' classified according to their profession from ancient times. The parents of our patient had migrated from the Multan region of Pakistan back to India at the time of partition, and are presently residing in the hilly region of Uttar Pradesh ( Fig. 1). There was no history of consanguinity in the family members presented in the pedigree chart ( Fig. 2). 1 Political map of India showing the neighboring countries, location of the patient's home in the state of Uttar Pradesh (U.P), and Multan from where the parents of the patient had migrated 2 Pedigree chart of the BS child The patient's father (39 years) and mother (35 years) were apparently normal and had four children. The eldest child is a normal 14‐year‐old girl. The second was a girl who died at the age of 2 years, presumably of a similar ailment. The third is a normal 11‐year‐old boy, and the last is the 6‐year‐old boy brought to our clinic. A similar problem has been said to exist in a 15‐year‐old male paternal cousin of the patient, but he has not been examined by us as he does not reside in the area. Physical examination of the patient revealed an alert and active boy with a pleasing personality, but an irritable mood. He had definite stunted growth, and his body weight (10 kg), height (91 cm), and head circumfer...

Clinical and laboratory findings in 8 patients with Bloom's syndrome

“…7 Some other minor clinical signs as "café au lait" spots were found in more than half of cases and German series. 6 Achromic patches have been reported by several authors 2,6,8 and discovered in 3 of our patients, they differ from the ashleaf-shaped macules described in tuberous sclerosis.…”

“…The gene responsible for BS has been mapped to chromosome 15 (15q26-1) which is closely linked to the proto-oncogene FES, and has been identified as a DNA helicase. 2,14,15 Chromosomal instability is manifest by an increase in the frequency of chromosome breakage and somatic recombination, which associated with immunologic deficiency is a predisposing factor to develop cancer. 16 The risk of occurrence of neoplasia is a major concern for BS patients.…”

Dominant Negative Mutations Affect Oligomerization of Human Pyruvate Kinase M2 Isozyme and Promote Cellular Growth and Polyploidy

“…The observation of two novel mutations in the ISCD region of PKM 2 accounting for its reduced activity in BS cells (18,19) followed the discovery of mutant BLM gene as an etiological factor for the syndrome (29). Incidentally, the defective BLM protein does not explain a number of clinical symptoms observed in the syndrome (30).…”

“…Hence, its role is implicated in cancer progression (14). Because any known aberration of PKM 2 is not yet observed in more than one naturally occurring pathological condition, its role as a "metabolic modulator" has remained enigmatic.This study deals with two missense mutations detected by us from a patient with BS, prone to various types of cancers at early age, and a BS cell line (18,19). Both K422R and H391Y mutant proteins individually were shown to maintain tetrameric structure, despite mutations in the ISCD domain, while showing a differential loss of activity.…”

“…This study deals with two missense mutations detected by us from a patient with BS, prone to various types of cancers at early age, and a BS cell line (18,19). Both K422R and H391Y mutant proteins individually were shown to maintain tetrameric structure, despite mutations in the ISCD domain, while showing a differential loss of activity.…”