A number sign (#) is used with this entry because primary microcephaly-6
(MCPH6) is caused by homozygous mutation in the gene encoding
centromeric protein J (CENPJ; 609279).
For a phenotypic description and discussion of genetic heterogeneity of
primary microcephaly, see MCPH1 (251200).Darvish et al. (2010) reported 2 affected individuals from a
consanguineous Iranian family with autosomal recessive primary
microcephaly. In addition to severe mental retardation and microcephaly
(-4 to -6 SD), the patients had additional features, including small
ears, hypertelorism, strabismus, notched nasal tip, seizures, joint
stiffness, and wheelchair requirement.
Sajid Hussain et al. (2013) reported 10 patients from 3 consanguineous
Pakistani families with primary microcephaly (-8 to -17 SD) between ages
7 and 30 years. Most of the patients were unable to speak or write.
The transmission pattern in the families with MCPH6 reported by Darvish
et al. (2010) and Sajid Hussain et al. (2013) was consistent with
autosomal recessive inheritance.
Leal et al. (2003) reported a novel locus, MCPH6, for autosomal
recessive primary microcephaly, mapping to 13q12.2, in a Brazilian
family. The minimal critical regions spanned 6 Mb between 2 markers with
a maximum 2-point lod score of 6.25.
By homozygosity mapping, Darvish et al. (2010) found linkage to the
MCPH6 locus in 5 of 112 consanguineous Iranian families with primary
In affected members of 3 families with MCPH6, of which 1 was the
Brazilian family previously described by Leal et al. (2003) and 2 were
Pakistani, Bond et al. (2005) identified a homozygous mutation in the
CENPJ gene (609279.0001-609279.0002, respectively). Each mutation was
absent from 380 northern Pakistani control chromosomes, showed the
expected disease segregation in families, and was not present in
chimpanzee, gorilla, orangutan, gibbon, mouse, or rat.
In affected members of a Pakistani family with MCPH6, Gul et al. (2006)
identified homozygosity for a 4-bp deletion in the CENPJ gene
In 2 affected members of a consanguineous Iranian family with primary
microcephaly, Darvish et al. (2010) identified a homozygous mutation in
the CENPJ gene (T821M; 609279.0005).
In 10 patients from 3 consanguineous Pakistani families with MCPH6,
Sajid Hussain et al. (2013) identified a homozygous truncating mutation
in the CENPJ gene (609279.0001). The mutations, which were found by
linkage analysis followed by Sanger sequencing of the candidate gene,
segregated with the disorder in the families. The families were
ascertained from a larger cohort of 57 consan...
HEAD AND NECK:
Microcephaly (head circumference -7 to -17 S.D.)
[Central nervous system];
Mental retardation, moderate;
Small cerebral cortex
Onset at birth
Caused by mutation in the centromeric protein J gene (CENPJ, 609279.0001)