复旦大学：《医学遗传学 Medical Genetics》课程教学资源（学习报告）Jean - Xeroderma Pigmentosa

Genetic Disease By: Jean Liu D:o8301016041

Genetic Disease By: Jean Liu ID: 08301016041

General Facts e Caused by an abnormality in an individuals genome e Can also be caused by environmental factors e The abnormality can range from minuscule to major 6 Point mutation (P)-insertion/deletion entirely inside one gene G Deletion(D)-removal of a gene or genes e C-whole chromosome extra, missing or both 6 Trinucleotide repeat disorder(T)-gene is extended length

General Facts Caused by an abnormality in an individual’s genome Can also be caused by environmental factors The abnormality can range from minuscule to major Point mutation (P) – insertion/deletion entirely inside one gene Deletion (D) – removal of a gene or genes C – whole chromosome extra, missing or both Trinucleotide repeat disorder (T) – gene is extended in length

Xeroderma Pigmentosum What Is It to Very rare inherited skin disorder e A person is highly sensitive to the sunlight(photosensitive) e Autosomal recessive genetic disorder 6 DNA repair - ability of repair damage caused by ultraviolet (UV) light e Six times more common in Japanese people than in other groups e Around 1 in 40,0oo e Equal numbers of male and female patients Less than 40% of individuals with XP survive beyond age 20 years Those with milder disease may survive beyond middle age Malignancy -medical condition that can progress, potentially result in death; eg: tumors

Very rare inherited skin disorder A person is highly sensitive to the sunlight (photosensitive) Autosomal recessive genetic disorder DNA repair – ability of repair damage caused by ultraviolet (UV) light Six times more common in Japanese people than in other groups Around 1 in 40,000 Equal numbers of male and female patients Less than 40% of individuals with XP survive beyond age 20 years Those with milder disease may survive beyond middle age Xeroderma Pigmentosum What Is It ? * Malignancy – medical condition that can progress, potentially result in death; eg: tumors

Xeroderma Pigmentosum Types Type Gene Locus Absent or minimal Type A, I, XPA XPA 9q22.3 DNA repair activity Type B, Il, XPB XPB 2q21 Few patients Most common, 1/3 Type C,Ⅲ1,XPC XPC 3q25 of all patients XPD Second most Type D,ⅣV,XPD ERCC6 19q13.2-q133,10q11 common Type E, V, XPE DDB2 11p12p11 Type F, VI, XPF ERCC4 16p1331313 RAD2 Type G, Vil, XPG ERCC 13q33 Dominant Type

Type Gene Locus Type A, I, XPA XPA 9q22.3 Absent or minimal DNA repair activity Type B, II, XPB XPB 2q21 Few patients Type C, III, XPC XPC 3q25 Most common, 1/3 of all patients Type D, IV, XPD XPD ERCC6 19q13.2-q13.3, 10q11 Second most common Type E, V, XPE DDB2 11p12-p11 Type F, VI, XPF ERCC4 16p13.3-p13.13 Type G, VII, XPG RAD2 ERCC5 13q33 Dominant Type Xeroderma Pigmentosum Types

Xeroderma Pigmentosum How is it inherited eo Genetic Condition Autosomal recessive E Can be passed from Carrier Carrier father mother eneration to generation in g co Autosomal recessive inheritance patter ■ Unaffected Mutation must be present Affected in both copies of the gene cArrier G Carrier -one copy of the 0 gene mutation e When both parents are carrier, there is a 25% chance that the child will be affected Unaffected Carrier Carrier Affected son daughter son daughter U. S National Library of Medicine

Genetic Condition Can be passed from generation to generation in Autosomal recessive inheritance patter Mutation must be present in both copies of the gene Carrier – one copy of the gene mutation When both parents are carrier, there is a 25% chance that the child will be affected Xeroderma Pigmentosum How is it inherited ?

Xeroderma Pigmentosum Symptoms Eo Skin E Eyes e Neurological

Skin Eyes Neurological Xeroderma Pigmentosum Symptoms

Xeroderma Pigmentosum Skin Symptoms E Severe sunburn after a short sun exposure e May last for several weeks Usually happens during a child's first exposure to the sun e Development of freckles at an early age E Irregular dark spots e Thin skin e Excessive dryness of the skin Premature aging of skin, lips, eyes, mouth and tongue e More than 1, ooo times the risk of developing skin cancer

Xeroderma Pigmentosum Skin Symptoms Severe sunburn after a short sun exposure May last for several weeks Usually happens during a child’s first exposure to the sun Development of freckles at an early age Irregular dark spots Thin skin Excessive dryness of the skin Premature aging of skin, lips, eyes, mouth and tongue More than 1,000 times the risk of developing skin cancer

Xeroderma Pigmentosum Eye Symptoms Occur nearly 80% of the patients G Eyes are very sensitive to the sun(photophobia) e Irritated Bloodshot e Cloudiness of the cornea e Darkening of the skin of the eyelids

Occur nearly 80% of the patients Eyes are very sensitive to the sun (photophobia) Irritated Bloodshot Cloudiness of the cornea Darkening of the skin of the eyelids Xeroderma Pigmentosum Eye Symptoms

Xeroderma Pigmentosum Neurological Symptoms e Only occur in 20-30% of people with XP t Tend to get worse over time e Hearing loss Normal head size Microcephaly e Microcephaly Spastic muscles eg Stiffness or tightness of the muscles Seizures e Intellectual impairment g Poor coordination BADAM

Only occur in 20-30% of people with XP Tend to get worse over time Hearing loss Microcephaly Spastic muscles Stiffness or tightness of the muscles Seizures Intellectual impairment Poor coordination Xeroderma Pigmentosum Neurological Symptoms

Xeroderma Pigmentosum Classifications e Mild 6 Light brown freckles on face 4 Moderate Dark brown freckles on face Burning on exposed parts of the body e Photophobia eo Severe Serious dark brown freckles Burning on exposed/unexposed parts of the body eo Cutaneous changes e Ocular changes

Mild Light brown freckles on face Moderate Dark brown freckles on face Burning on exposed parts of the body Photophobia Severe Serious dark brown freckles Burning on exposed/unexposed parts of the body Cutaneous changes Ocular changes Xeroderma Pigmentosum Classifications