KEGG DISEASE: Microcephaly, growth restriction, and increased sister chromatid exchange

DISEASE: Microcephaly, growth restriction, and increased sister chromatid exchange

Entry

H02492                      Disease

Name

Microcephaly, growth restriction, and increased sister chromatid exchange

Subgroup

Bloom syndrome [DS:H01346]

Description

Microcephaly, growth restriction, and increased sister chromatid exchange (MGRISCE) is characterized by prenatal onset growth restriction and microcephaly. Diagnostically, a hallmark feature is the presence of increased sister chromatid exchanges on cytogenetic testing. MGRISCE1, caused by biallelic mutations in BLM, is known as Bloom syndrome [DS:H01346]. Recently, MGRISCE2, caused by mutations in TOP3A, has been reported. TOP3A encodes topoisomerase III alpha, which binds to BLM as part of the BTRR complex, and promotes dissolution of double Holliday junctions arising during homologous recombination.

Category

Congenital malformation

Brite

Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
  Multiple developmental anomalies or syndromes
   LD20  Syndromes with central nervous system anomalies as a major feature
    H02492  Microcephaly, growth restriction, and increased sister chromatid exchange
Pathway-based classification of diseases [BR:br08402]
Replication and repair
  nt06506  Double-strand break repair
   H02492  Microcephaly, growth restriction, and increased sister chromatid exchange

Pathway

hsa03440

Homologous recombination

hsa03460

Fanconi anemia pathway

Network

nt06506 Double-strand break repair

Gene

(MGRISCE1) BLM [HSA:641] [KO:K10901]
(MGRISCE2) TOP3A [HSA:7156] [KO:K03165]

Other DBs

ICD-11:

LD20.2

OMIM:

210900 618097

Reference

PMID:4140506

Authors

Chaganti RS, Schonberg S, German J

Title

A manyfold increase in sister chromatid exchanges in Bloom's syndrome lymphocytes.

Journal

Proc Natl Acad Sci U S A 71:4508-12 (1974)
DOI:10.1073/pnas.71.11.4508

Reference

PMID:23928670 (MGRISCE1)

Authors

Renes JS, Willemsen RH, Wagner A, Finken MJ, Hokken-Koelega AC

Title

Bloom syndrome in short children born small for gestational age: a challenging diagnosis.

Journal

J Clin Endocrinol Metab 98:3932-8 (2013)
DOI:10.1210/jc.2013-2491

Reference

PMID:30057030 (MGRISCE2)

Authors

Martin CA, Sarlos K, Logan CV, Thakur RS, Parry DA, Bizard AH, Leitch A, Cleal L, Ali NS, Al-Owain MA, Allen W, Altmuller J, Aza-Carmona M, Barakat BAY, Barraza-Garcia J, Begtrup A, Bogliolo M, Cho MT, Cruz-Rojo J, Dhahrabi HAM, Elcioglu NH, Gorman GS, Jobling R, Kesterton I, Kishita Y, Kohda M, Le Quesne Stabej P, Malallah AJ, Nurnberg P, Ohtake A, Okazaki Y, Pujol R, Ramirez MJ, Revah-Politi A, Shimura M, Stevens P, Taylor RW, Turner L, Williams H, Wilson C, Yigit G, Zahavich L, Alkuraya FS, Surralles J, Iglesias A, Murayama K, Wollnik B, Dattani M, Heath KE, Hickson ID, Jackson AP

Title

Mutations in TOP3A Cause a Bloom Syndrome-like Disorder.

Journal

Am J Hum Genet 103:221-231 (2018)
DOI:10.1016/j.ajhg.2018.07.001

LinkDB

» Japanese version

DISEASE: Bloom syndrome

Entry

H01346                      Disease

Name

Bloom syndrome;
MGRISCE1

Supergrp

Immunodeficiency associated with DNA repair defects [DS:H00094]
Disorders of adaptive immunity [DS:H02526]
Primary immunodeficiency disease [DS:H01725]
Defects in RecQ helicases [DS:H00296]
Microcephaly, growth restriction, and increased sister chromatid exchange [DS:H02492]

Description

Bloom syndrome is a rare autosomal recessive genetic disorder due to mutation in BLM (RecQ protein-like 3). This disease is characterized by severe growth deficiency, an erythematous and photosensitive facial rash, dysmorphic features such as microcephaly and malar hypoplasia, immunodeficiency and a high predisposition to various types of cancer. The function of BLM as a helicase and its role during the regulation of homologous recombination (HR) is well characterized. Recently, the role of BLM as a DNA damage sensor has been revealed.

Category

Congenital malformation

Brite

Human diseases in ICD-11 classification [BR:br08403]
04 Diseases of the immune system
  Primary immunodeficiencies
   4A01  Primary immunodeficiencies due to disorders of adaptive immunity
    H01346  Bloom syndrome
Pathway-based classification of diseases [BR:br08402]
Replication and repair
  nt06506  Double-strand break repair
   H01346  Bloom syndrome

Pathway

hsa03440

Homologous recombination

hsa03460

Fanconi anemia pathway

Network

nt06506 Double-strand break repair

Gene

BLM [HSA:641] [KO:K10901]

Comment

Disorder of DNA repair system

Other DBs

ICD-11:

4A01.31

MeSH:

D001816

OMIM:

210900

Reference

PMID:23543275

Authors

Manthei KA, Keck JL

Title

The BLM dissolvasome in DNA replication and repair.

Journal

Cell Mol Life Sci 70:4067-84 (2013)
DOI:10.1007/s00018-013-1325-1

Reference

PMID:21050475

Authors

Tikoo S, Sengupta S

Title

Time to bloom.

Journal

Genome Integr 1:14 (2010)
DOI:10.1186/2041-9414-1-14

Reference

PMID:19661064

Authors

Kikuchi K, Abdel-Aziz HI, Taniguchi Y, Yamazoe M, Takeda S, Hirota K

Title

Bloom DNA helicase facilitates homologous recombination between diverged homologous sequences.

Journal

J Biol Chem 284:26360-7 (2009)
DOI:10.1074/jbc.M109.029348

Reference

PMID:23928670

Authors

Renes JS, Willemsen RH, Wagner A, Finken MJ, Hokken-Koelega AC

Title

Bloom syndrome in short children born small for gestational age: a challenging diagnosis.

Journal

J Clin Endocrinol Metab 98:3932-8 (2013)
DOI:10.1210/jc.2013-2491

LinkDB

» Japanese version

DISEASE: Defects in RecQ helicases

Entry

H00296                      Disease

Name

Defects in RecQ helicases

Subgroup

Bloom's syndrome [DS:H01346]
Werner's syndrome [DS:H01733]
Rothmund-Thomson syndrome [DS:H01734]
RAPADILINO syndrome [DS:H00965]
Baller-Gerold syndrome

Description

RecQ helicases have crucial roles in the maintenance of genome stability. In humans, it is known that deficiencies in three of the five human RecQ helicases cause genetic disorders characterized by cancer predisposition, premature aging and developmental abnormalities. These disorders are Bloom's syndrome (BS), Werner's syndrome (WS), and Rothmund-Thomson syndrome (RTS), which are caused by mutations in BLM, WRN and RECQL4, respectively. Despite the apparent structural and biochemical similarities between the BLM, WRN and RECQL4 proteins, the phenotypes of BS, WS and RTS are different, suggesting that each disease pathway is functionally distinct to some extent. BS is characterized by most prominently, a predisposition to all types of cancers. WS is characterized by the premature development of features that resemble aging. RTS is characterized by skin and skeletal abnormalities, signs of premature aging, and cancer predisposition, especially to osteosarcomas. Recent research has shown many connections between all three proteins and the regulation of excess HR (Homologous recombination). It was also indicated that BLM is involved in repair of stalled DNA replication forks, and that WRN is required for telomere maintenance. Mutations in RECQL4 also associate with 2 additional syndromes, Rapadilino and Baller-Gerold syndrome.