Cystic Fibrosis (
(CF) is a common autosomal
recessive disorder, which affects the entire body, causing progressive
disability and often early death. The hallmark symptoms of cystic fibrosis are
salty tasting skin, poor growth and poor weight gain despite a normal food
intake, accumulation of thick, sticky mucus, frequent chest infections and
coughing or shortness of breath. CF is caused by a mutation in the gene for the
protein cystic fibrosis transmembrane conductance regulator (CFTR). This gene
is required to regulate the components of sweat, digestive juices, and mucus.
The most common mutation, ?F508, is a deletion (?) of three nucleotides that
results in a loss of the amino acid phenylalanine (F) at the 508th position on
the protein. This mutation accounts for two-thirds (66-70%) of CF cases
worldwide CF is most common among Caucasians and Ashkenazi Jews; one in 25
people of European descent carry one mutant copy of
The estimated prevalence of CF is 1/43,321 to 1/100,323 in Indian population.
The carrier frequency of F508del mutation in the Indian population has been
estimated to be 1/238 (0.42%). Frequency of CF patients homozygous for F508del
mutation is 1/228,006.
a group of inherited or acquired disorders of certain enzymes in
the heme bio-synthetic pathway, manifesting with either neurological
complications or skin problems (or occasionally both). They are broadly
classified as acute (hepatic) porphyrias and cutaneous
(erythropoietic) porphyrias according to the site of accumulation or
overproduction of porphyrins. Acute intermittent porphyria (AIP), one of
the most common form of porphyria (
is rare autosomal dominant metabolic
disorder (very rarely homozygous) characterized by a deficiency of
the enzyme porphobilinogen deaminase, the responsible gene being
The database currently holds the relevant data of PBGD gene only pertaining to
Rhizomelic Chondrodysplasia Punctata type 1 (
(also known as "Autosomal recessive chondrodysplasia punctata type 1”), is a
rare, multisystem developmental disorder characterized by dwarfism due to
systemic shortening of the proximal bones (i.e. rhizomelia), specific
radiologic abnormalities, joint contractures, congential cataracts, ichthyosis,
and severe mental retardation. It is caused by mutations in the PEX7 gene,
which encodes the peroxisomal type 2 targeting signal (PTS2) receptor.
H syndrome (
syndrome is a recently reported autosomal-recessive disorder characterized by
cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, heart
anomalies, hearing loss, hypogonadism, short stature, hallux valgus, and fixed
flexion contractures of the toe joints and the proximal interphalangeal joints.
It is caused by mutations in the SLC29A3
gene, which encodes the equilibrative nucleoside transporter hENT3.
Biotidinase Deficiency (
MIM: 253260 )
deficiency is an autosomal recessive metabolic disorder where the body is
unable to reuse and recycle biotin. This disorder is classified as a multiple
carboxylase deficiency, a group of disorders characterized by impaired activity
of certain enzymes that depend on biotin. The signs and symptoms appear within
the first few months of life, but the age of onset varies. Sverely affected
sunjects often have seizures, weak muscle tone (hypotonia), breathing problems,
and delayed development. If left untreated, the disorder can lead to hearing
loss, eye abnormalities and loss of vision, problems with movement and balance
(ataxia), skin rashes, hair loss (alopecia), and a fungal infection called
candidiasis. Mutations in the BTD gene cause biotinidase
Costello Syndrome (
MIM: 218040 )
syndrome, also called faciocutaneoskeletal syndrome or FCS syndrome, is a rare
multisystem genetic disorder characterized by delayed development and mental
retardation, distinctive facial features, unusually flexible joints, and loose
folds of extra skin, especially on the hands and feet, heart abnormalities,
structural heart defects, and overgrowth of the heart muscle etc. Infants with
Costello syndrome may be large at birth, but grow more slowly than other
children and have difficulty feeding. Later in life, people with this condition
have relatively short stature and many have reduced levels of growth hormones.
This is caused by mutations in the HRAs gene and the disease is
inherited in autosomal dominant mode.
Nance-Horan Syndrome (
MIM: 303250 )
syndrome (NHS) is a rare but probably underdiagnosed disorder characterized by
the association in male patients of congenital cataracts with microcornea,
dental anomalies and facial dysmorphism. Intellectual impairment is observed in
about 30% of cases with inter- and intrafamilial variability. NHS is caused by
mutations in the NHS gene and is transmitted in an X-linked dominant mode.
Frasier syndrome (
MIM: 136680 )
is a rare disorder characterized by genital (normal female external genitalia,
streak gonads, XY karyotype and frequently gonadoblastoma) and renal
manifestations (childhood proteinuria and nephritic syndrome, characterized by
nonspecific focal and segmental glomerular sclerosis, progressing to end-stage
renal failure in adolescence or early adulthood).
Renal Cysts and Diabetes (RCAD) Syndrome
MIM: 137920 )
Cysts and Diabetes (RCAD) Syndrome is caused by mutation in the gene
encoding hepatocyte nuclear factor-1-beta (TCF2, or HNF1B).
is an autosomal dominant disorder comprising
nondiabetic renal disease resulting from
abnormal renal development, and diabetes, which in some cases occurs
earlier than age 25 years (MODY). The renal disease is highly
variable and may also accompany different abnormalities of the genital tract.
Neurodegeneration with Brain Iron Accumulation, Type 1
with Brain Iron Accumulation type 1, NBIA 1 (
MIM: 234200 )
is an autosomal recessive neurological/metabolicdisorder characterized by
progressive iron accumulation within the basal ganglia leading to motor
disabilities, speechdisorders, intellectual impairments, psychiatric problems,
depression and vision loss.Motor
disabilities gains severity with increasing age and the condition of the
patient worsens. Mutations in the PANK2is the gene responsible for this
disorder and is mapped to chromosome 20p. The mutations in the PANK2 gene cause
paucity in the production of coenzyme A, which causes iron accumulation in the
basal ganglia of brain that leads to neurodegeneration.
It is estimated to affect 1 to 3 per million people worldwide.
Terminal 4q deletion syndrome
4q deletion (4q31->qter) syndrome is a rare chromosomal abnormality, often
arises de novo. Patients are severely affected with the characteristic facial,
skeletal, and developmental anomalies; many patients die at infancy.
Chronic infantile neurological cutaneous articular (CINCA) syndrome (
infantile neurological cutaneous articular (CINCA) syndrome is a rare
congenital auto inflammatory disorder characterized by persistent cutaneous
symptoms, meningitis, joint deformities with recurrent fever and inflammation.
It is caused by mutations in the CIAS1gene,
mapped to chromosome 1q44.
Congenital Generalized Lipodystrophy, Type 2 (
Generalized Lipodystrophy, type 2, also known as
Berardinelli-Seip syndrome, is a rare form of autosomal recessive
metabolic disorder characterized by lack of overall adipose tissuein the body
along with extreme insulin
resistance, hypertriglyceridemia, hepatic steatosis, early onset of diabetesand
mental and intellectual impairment.
estimated prevalence of CGL Type 2 is 1 in 10 million people worldwide. BSCL2 (
the gene responsible for this disorder, has been reported that is mapped to
chromosome 11q. BSCL2 mutants in general exhibit
premature mortality with a range of 4 months to 35 years of age.
Allgrove syndrome (
syndrome is a rare autosomal recessive congenital disease. The candidate gene
is AAAS, which is mapped to chromosome 12q13.13 (AAAS;
The clinical manifestations include achalasia, alacrima, autonomic neuropathy
and addisonianism, with significant impairment of the central nervous system,
ACTH-resistant adrenal insufficiency, altered skin pigmentation, iron
deficiencies, abnormal peristalsis of the intestine, delay in motor and speech
developments, ataxia, anisocoria and progressive loss of cholinergic functions.
Only 4 individuals with no specified ethnicity have been studied in India from
South Indian population. The disease is prevalent in consanguineous
Glycogen storage disease Ia
storage disorder Ia, caused by mutations in G6PC gene, is an autosomal
recessive disorder causing accumulation of glycogen in different organs. It
typically manifests during the first year of life with severe hypoglycemia and
hepatomegaly. The disorder is characterized by growth retardation, delayed
puberty, lactic acidemia, hyperlipidemia, hyperuricemia and other features.
Hypohidrotic-Hair-Tooth type Ectodermal Dysplasia 10B (
type Ectodermal Dysplasia 10B is an autosomal recessive congenital disorder
caused by mutations in the EDAR/Ectodysplasin Anhidrotic Receptor gene. The
disease is characterized by a triad of signs comprising sparse hair
(hypotrichosis), abnormal or missing teeth (anodontia or hypodontia) and
inability to sweat (anhidrosis or hypohidrosis).
X-linked hypohidrotic ectodermal dysplasia 1 (
hypohidrotic ectodermal dysplasia 1 caused by mutations in the ED1 gene, is the
most frequent form of hypohidrotic ectodermal dysplasia. It is an X-linked
recessive congenital disorder manifesting only in males. The disorder is
characterized by a triad of signs comprising sparse hair (hypotrichosis),
abnormal or missing teeth (anodontia or hypodontia) and inability to sweat
(anhidrosis or hypohidrosis). Dryness of the skin, eyes, airways, mucous
membranes and various dysmorphic features may also be present in the patients.
Chronic Pancreatitis (
pancreatitis is a disorder characterized by recurrent episodes of inflammation
of the pancreas (pancreatitis) manifesting as occasional or frequent abdominal
pain of varying severity, fever,
pancreatic insufficiency, diabetes
mellitus and pancreatic calculi.Chronic pancreatitis
may be caused by mutations in the cationic trypsinogen gene PRSS1 (
and the SPINK1 gene (
and can also be associated with mutations in the cystic fibrosis gene (CFTR;
and CTRC gene (
Mutations in the Calcium-Sensing Receptor gene (CASR;
have also been reported in association with chronic pancreatitis.
database presently holds the data for SPINK1, CFTR, CTRC and CASR mutations.
Congenital erythropoietic porphyria (Gunther disease) (
erythropoietic porphyria (Gunther disease) is an autosomal recessive disease
caused by mutation in the uroporphyrinogen III synthase gene (UROS,
The porphyrias are group of diseases characterized by defects in heme
synthesis, resulting in the accumulation and increased excretion of porphyrins
or porphyrin precursors. They manifest as light-sensitization and severe skin
damage, hemolytic anemia, jaundice, hepatosplenomegaly, bleeding and
Dilated cardiomyopathy with woolly hair and keratoderma (Carvajal syndrome) (
cardiomyopathy with woolly hair and keratoderma (Carvajal syndrome) is an
autosomal recessive disease caused by
mutation in the DSP gene (
Patients have wooly hair since birth and keratoderma appears a little later.
Dilation of cardiac chambers and other cardiac changes might lead to congestive
heart failure and death.
Focal dermal hypoplasia (Goltz syndrome) (
hypoplasia is an X-linked dominantdisease
caused by mutations in the PORCN gene (
), causing in utero lethality in males.
It is characterized by atrophy and linear
pigmentation of the skin, herniation of fat through the dermal defects, and
multiple papillomas of the mucous membranes or skin. Various digital, oral and
ocular anomalies along with striated bones are also common manifestations.