The Principles of Clinical Cytogenetics - Extra Materials - Springer

526 Jin-Chen Wang
cause SRS (183). One region at 7p11.2-p13 contains an imprinted gene, GRB10 (growth factor
receptor-binding protein 10), a known growth suppressor that is expressed on the maternal allele
and is, therefore, a strong candidate gene for SRS (184–186). A second region at 7q31-qter contains
the two other imprinted genes on chromosome 7 identified to date: PEG1/MEST and γ2-COP.
The role of these two genes in SRS is not yet clear (179,187). Maternal UPD 7 clearly has an
imprinting effect.
upd(7)pat
Two cases of paternal isodisomy for the entire chromosome 7 have been reported. One patient had
recessive congenital chloride wasting diarrhea with normal growth and development (188). The other
patient had cystic fibrosis as a result of inheriting two copies of the ∆F508 mutation from his father.
This patient also had complete situs inversus and immotile cilia with growth retardation and significant
respiratory disease (189). In addition, two patients had paternal isodisomy 7p and maternal
isodisomy 7q (190,191). These two patients had similar phenotypes that resembled that seen in maternal
UPD 7, and their growth retardation was considered to be a result of maternal isodisomy for 7q. It
is not clear whether paternal UPD 7 confers an imprinting effect.
upd(8)mat
One case of maternal isodisomy for the entire chromosome 8 has been reported (192). The patient
was a 39-year-old male with normal appearance, stature, and intelligence. He had early-onset ileal
carcinoid, slight thoracic scoliosis, and numerous pigmented nevi. More cases are needed before a
conclusion can be drawn as to whether maternal UPD 8 has an imprinting effect.
upd(8)pat
A single case of paternal uniparental isodisomy for chromosome 8 has been reported (193). This
51 / 2-year-old girl had normal development and lipoprotein lipase (LPL) deficiency as a result of a
mutation of the LPL gene. The patient was ascertained because of a diagnosis of chylomicronemia.
The father was a heterozygous carrier for the same mutation. It appears that normal development can
occur in paternal UPD 8 and that an imprinting effect of this UPD might not exist.
upd(9)mat
Six cases of maternal UPD for chromosome 9 have been reported. Two patients had recessive
cartilage hair hypoplasia, a disorder that maps to the short arm of chromosome 9 (194). Two homozygotic
female twins had Leigh syndrome as a result of inheriting two copies of the mutated SBRF-1
gene from their mother (195). Both twins died of respiratory failure at age 3. No gross dysmorphic
features or malformations were noted apart from Leigh syndrome. One case involved a fetus associated
with confined placental mosaicism (see Chapter 12) for trisomy 9 (196). Pathological examination
of the abortus was not possible. Another 34-year-old healthy woman with recurrent spontaneous
abortions had isochromosomes of the short and long arms of chromosome 9 [i(9)(p10),i(9)(q10); see
Chapters 3 and 9]. Molecular analysis demonstrated maternal isodisomy (197). The available data
indicate that maternal UPD 9 might not have an imprinting effect.
upd(10)mat
A single case of prenatally diagnosed maternal UPD for chromosome 10 associated with confined
placental mosaicism (see Chapter 12) has been reported (198). The infant was phenotypically and
developmentally normal at 8 months of age. Two other cases of maternal UPD 10 reported were
associated with either a marker chromosome 10 or a trisomy 10 cell line and the abnormal phenotypes
were attributed to the karyotypic abnormalities. There is no evidence to date that this UPD
confers an imprinting effect.